3/24/2018

Microbiological CL Contaminants
Pathogenic micro-organisms: Fungus (Aspergillis niger)
• Bacteria in SCL fracture (low mag)

• Viruses
Lens care regimen & systems • Protozoans
• tap water used on lenses?
• Fungi (Image: Michael Hare, AUSTRALIA)

• occupational hazard (farmer?)

Lens deposits & contamination

Pseudomonas aeruginosa
(high-mag SEM image)

Microbiological CL Contaminants:
What Are CL Contaminants? Fungal
• Biological

(Image: Michael Hare,

• Relatively uncommon

AUSTRALIA)
• largely organic
• Aspergillus sp., Candida albicans,
• some inorganic
Fusarium sp., & Penicillium sp.
• Microbiological
are the most common fungi
• pathogenic Aspergillus niger
– but Candida sp.   infections (hydrogel CL,
• non-pathogenic retro-illumination)
• Importantly,
• Environmental
– Candida parasilosis  catalase
• largely inorganic (Image: Michael Hare, AUSTRALIA)
Candida albicans
hydrogel CL,
Compound deposit –  efficacy of peroxide care systems
• organic possible Jelly bumps (mainly lipid), protein, iron
(direct illumination)

( corroding in situ ) • Fungal biomass on CLs  over time

A fungus
(retro-illumination)

Biological CL Contaminants MICROBIOLOGICAL CL CONTAMINATION :

BACTERIAL
Largely organic
• Tear film components
• Cellular debris
• • SCLs with deposits of Mucin, lactoferrin,
‘Cracked’ protein films

Other body-sourced contaminants:

• skin lipids from eyelids
lysozyme, IgA, and
• finger-borne oils & soilage
mixtures of these
• Discolourations of biological origin
 Pseudomonas Aeruginosa
Inorganic also possible, e.g. NaCl
crystals (from tear evaporation)

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MICROBIOLOGICAL CL CL Deposits & Lens Care

CONTAMINATION : BACTERIAL
Routine lens care procedures reduce deposits but
• In vitro :
are unable to eliminate them completely

– All SiHy CLs attracted slightly more negative-strain

Staphylococcus epidermidis than did
conventional hydrogel CLs
Jelly bumps in direct & marginal
retro-illumination
(high magnification, slit-lamp photo)
Bacterial colony on CL surface
(medium magnification, laboratory
microscope photo)

Environmental CL Contaminants: CL Deposits: Some Extreme Examples

Iron (Fe)
Left: Rust particle on a hydrogel, particle
embedded. Ferrous (Fe++) & ferric (Fe+++)
oxide deposits appear as blue (below) or
yellow/orange (left) respectively. Little
discomfort results thanks to protein coating

Lipid Lipid Lipid-Calcium

Right: Rust spot (effect of a corroding iron [Fe]

particle in the surface of a hydrogel CL). Iron
particle dislodged, pit remains

Protein Poor wetting

What Are CL Deposits? CL Deposits: Influential Factors

Translucent lipid & Bacteria: In this case
[calcium, protein, or
mucin] combination
deposit on a hydrogel CL - on a GP CL SEM image
‘Jelly bumps’
If white, the term ‘lens
calculi’ has been used
(high-magnification slit-
lamp image)
Biofilm on a CL surface
Pseudomonas Preparation for microscopy
aeruginosa dehydrates the film hence
its crenated appearance
Biofilm is probably
polymicrobial SEM image
• Lens type:
• GP (including sclerals)
• hydrogel (categorized by ionicity & water content)
• silicone hydrogel (SiHy)
• Tear film:
• normal
• marginal dry eye/ dry eye
• ocular pathology (e.g. conjunctivitis)
• systemic disease (e.g. Sjögren’s Syndrome)
• Environmental factors:
• air quality
• water quality
• lens care products
• cosmetics, skin care products
• industrial environment (particulates, vapours)
• Replacement frequency:
• daily (DD)
• frequently (1-4 weeks)
• planned (3-12 months)
• unplanned (CLs failure or discomfort)

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The Tear Film: Proteins CL Deposits: Mucins

Meibomian Gland
>90 proteins have been identified in
human Meibomian gland secretions Other Sources
•
• Less literature on mucins cf. proteins or lipids
Tears •
Lacrimal gland
Accessory lacrimal glands:
(an incomplete list)
Lipocalin (formerly TSPA: has lipid-binding properties)
– Glands of Wolfring
– Glands of Krause
• Bacteria possess mucinolytic properties (by
Lysozyme
Lacritin • Mucus secreting glands proteolysis & glycolysis)
– goblet cells
Lactoferrin
Proline Rich protein, e.g. 4 •
– sub-surface vesicles
Blood vessels, e.g. albumin, • bacteria effective against intact & degraded
Ig A, E, G, M a blood serum protein, enters
Secretoglobins (mammaglobins) the tears by vessel leakage mucins
Prolactin-induced protein
Surfactant protein D
Albumin
• mucins  bacterial corneal adherence
Protein G
(Complement) C3, factor B, and C4 in open-eye and reflex tears AND • removal of mucins by their incorporation into CL
Clq, C3, factor B, C4, C5, and C9 in closed-eye tears
Lipophilin AC deposits may  control of the bacterial population
-globulin and to a lesser extent -globulin
Substance P
Dissolved mucin (e.g. MUC5AC) (very little)

Lysozyme Deposits: Removal Mucins Deposits: Management

• Method of choice: a proteolytic enzyme
(protease)
• To remove lysozyme deposits either:
• break the disulphide bridges between
cysteine amino acids (i.e. a cysteine
protease, e.g. papain), or…
• hydrolyse peptide bonds (i.e. serine
protease or carbonyl hydrolase, e.g.
subtilisin)
• In vitro lysozyme removal efficiency using a
conventional MPS: balafilcon A (60%) > etafilcon
A (25%) > lotrafilcon B (10%)
• If CLs due for replacement, discard them
• If not, clean lens thoroughly with a single-purpose CL cleaner
• an alcohol-based cleaner may be effective
• rinse thoroughly
• disinfect normally
• consider the use of an enzymatic cleaner containing a
amylase (e.g. pancreatin) that breaks down
polysaccharides (mucin is a mucopolysaccharide)
• If the problem is recurring and CLs are not due for
replacement, consider replacing the CLs more frequently

Protein Deposits: Management CL Deposits: Lipid

• Commonly, enzymatic protein removers
• Complete removal is unlikely
• in vitro, protein removal from hydrogel CLs is <50%
typically
(Image: D Goldsbury
• Removed protein is replaced rapidly NEW ZEALAND) Combined lipid & mucus Image: D Fonn, CANADA
deposit [GP]
• Partially unraveled proteins (denatured) exhibit 
adherence to biomaterials cf. native form. Therefore
more difficult to remove
• Protein removal required for CLs used for >1 month
• Regular CL replacement is the practical answer

(Image: D Pye AUSTRALIA

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CL Deposits: Lipid CL Discolourations

Lipid deposits: • Uncommon in modern CL practice
•  Meibomian glands • Organic (white or brown fungus) or inorganic (iron [Fe++ &
• Limited solubility in water,  solubility in some CL Fe+++])
materials
• Difficult or impossible to remove (some can be bleached)
• Especially N-VP-containing materials
• Can be innocuous or a threat
• Oily tears, thick lipid tear layer, & lens dry spots may
predispose CLs to  lipid deposition • Bound to CLs or may leach from them
• Poorly wetting GP surfaces more susceptible • May  progressively, or be the result of a one-off
• Appear as greasy, shiny, difficult-to-remove deposits event/exposure
• Commonly form complexes with mucins, proteins, • May be the result of lens material or deposit ageing (e.g.
and/or calcium yellowing of protein deposits)

The Tear Film: Lipids CL Discolourations continued…

Main Lipids: Meibomian Gland Other Sources
• Can be medications containing:
• Wax esters
• Cholesterol esters • Lacrimal gland • mercurial preservative (grey  to black)
• Lipid secreting lands
• Oleamide
• Di & Triacyl glycerols (little)
– Glands of Zeis • phenylephrine/epinephrine (black, grey,
– Glands of Moll
• Free cholesterol (<1%) Tears or brown)
(an incomplete list)
• tetracycline (yellow)
Wax esters
Cholesterol esters • phenolphthalein (pink)
Oleamide (cis-9-octadecenamide) • instill drops 10 min. before CLs
Mono, di, & triacyl glycerols
Free cholesterol • Sodium fluorescein stain most SCLs,
Phospholipids (polar lipids) esp. ionic materials
Ceramide • Rust spots/metal corrosion
Myristamide, palmitamide, stearamide, & erucamide
• Cosmetics, nicotine
• Smoke & fumes in workplace, dust,
chemical aerosols

Lipid Deposits: Management CL Deposits: Clinical Assessment

• Disposable CLs has seen the motivation to assess & analyze CL deposits
• Lipid deposits tend to be thick, oily, & disturbing visually decrease significantly
•  visual disturbances blink modulated • Simplest assessment methods (non-destructive):
• slit-lamp & direct illumination, CL on fingers/forceps, on-eye, or in a wet-
• effect likened to looking through a car windscreen smeared cell
with road grime • stereo microscope, CL in wet-cell/on a slide
• Alcohol-based, single-purpose CL cleaners are the ‘tool’ of choice • use of a grading scale
(availability has become an issue) SLIT-LAMP OBSERVATIONS
• With jelly bumps, replacement is the only option
• while removal is possible, a ‘matching pit’ remains in CL
• this fills rapidly with tear debris
• the deposit is replaced rapidly (patient-dependent)
Altered specular reflection
• an optical defect also results - front surface deposit Protein film in direct & Exaggerated discolouration
marginal retro-illumination when examining lens edge

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Some LCPs (Disinfectants)

CL Deposits: Clinical Assessment
continued...

Mascara & eyeliner on a GP lens

(pre-existing deposits may assist attachment)

Grading & Classification: Chemistry of SCLs: HEMA

Simple Clinical System
Slit-Lamp assessment of deposition: Many soft lens materials are HEMA, HEMA-based, or
• Grading scale: 0 to 4 • Area of coverage: contain HEMA
0 No deposition • 0 - 20%
1 Just detectable deposition • 20 – 40% HEMA Monomer
2 Mild deposition • 40 – 60%
3 Moderate deposition • 60 – 80%
• 80 - Complete Typically, HEMA
4 Severe deposition hydrogels have a water
content of about 39%
• Description: • Location:
• Size (mm)
• Front
• Thickness (surface only, <tear film, Hydroxy
=tear film, proud of tear film, »tear • Back Ethyl
film)
• In lens matrix Meth
• Layers (film-like, single, multi) Acrylate
• Position (o’clock, central, mid-
peripheral, peripheral, edge) Hydroxyl tail showing
the charged sites

Chemistry of SCLs: N-VP

Chemical entities may be added to  water content or alter other

physical or physiological properties, e.g.
N-VinylPyrrolidone (NVP [or pVP])

Care & Maintenance of Hydrogel & N-VP

Silicone Hydrogel Contact Lenses Typically, HEMA + N-VP

hydrogels have a water
content of about 55%

C4 N (variable # of) Rigid pyrrolidone ring

rotates about the N-C
Vinyl axis & has charged
Pyrrolidone sites

2016-June-24

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Chemistry of SCLs: MA
Hydrogel CLs: Cleaners
Other chemical entities may be added to  water content or alter other
Formulation (preservatives):
physical or physiological properties, e.g. Methacrylic Acid (MA)
• Preservative required if LCP not self-preserving
MA
– BIGUANIDE: For SCLs, polymeric biguanide, e.g. polihexanide (PHX,
Typically, HEMA + MA PAPB, PHMB), used because its molecular size (8 nm – Tonge et al.,
hydrogels have a water
content of about 42-60% 2001) limits CL matrix penetration – usually with EDTA & borate buffer
system to  antifungal efficacy
– QUATERNARY AMMONIUM COMPOUND. Currently, polymeric QACs
most common, e.g. polyquaternium-1 (PQ-1)
Methacrylic MA has its own hydroxyl
Acid tail with charged sites – sorbic acid has been used, now uncommon
– mercurials have also been used in the past but most regulatory &
environmental authorities have an aversion to mercury (Hg) compounds

Hydrogel CLs: Cleaners

Rinsing Solutions
Purpose: Purpose:
• Loosen &/or solubilize (& remove subsequently), • Adjunct to cleaning & protein removal processes
contaminants (including deposits) bound to, or simply • Remove contaminants loosened by cleaning step
located on, CL surfaces
• Kill &/or remove majority of viable & necrotic micro- • Remove traces of cleaner from CLs
organisms • Re-hydration of CLs
–  surviving micro-organisms   ‘margin of safety’ of –  comfort on insertion
disinfection step (i.e. disinfection is completed within
manufacturer’s Minimum Recommended Disinfection – restore lens parameters
Times [MRDTs]) • Adjunct to disinfection, just prior to CL insertion

Hydrogel CLs: Cleaners Rinsing Solutions

Formulation (possible excipient components): Formulation:

• Alcohol to render lipids soluble in water • Originally, normal (0.9%) saline

– bulk unpreserved (NOT recommended,  contamination risk,
• EDTA (EthyleneDiamine Tetraacetic Acid), calcium (Ca++)
especially wide-mouth bottles)
chelating agent, also enhances action of many common
– preserved saline (potential preservative sensitivity)
preservatives
– unit-dose, unpreserved saline (ideal)
• Buffer system to control pH
• MPSs & One-Bottle Systems (OBSs) ( number of LCPs required
• Agent(s) that adjust osmolality for safe lens wear)
• Mild abrasive (often a fine, insoluble polymer that aids
loosening or removal of adherent surface contaminants
Because of Acanthamoeba spp. & other micro-organisms, TAP WATER has NO
(CL surfaces not affected) Phillips & Czigler, 1985 RÔLE in the care of any type of CL (including GP CLs) or CL case

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Hydrogel CLs: Disinfectants Hydrogel CLs: Disinfectants

Current practice includes the following:
• Hydrogen peroxide (H2O2, usually 3% solution)
– 1-step system using a catalyst: platinum (Pt)
& carbon-coated disc,
– 2-step system using catalase tablet (or deploy a
1-step system but withhold neutralizing tablet
until CLs required)
colour indicators (e.g. cyanocobalamine
[Vitamin B12]) may be included to confirm
neutralization
Newer products are being formulated to target
Acanthamoeba spp. specifically, in anticipation of this
becoming mandatory, e.g.:
• PQ-1-based multi-purpose disinfecting solution (MPDS)
containing MyristAmidoPropyl Dimethylamine (MAPD, a.k.a.
Aldox® – an anti-acanthamoeba agent) has been available for
some time
• MPSs containing both PHX & PQ-1
• MPSs containing both alexidine dihydrochloride & PQ-1

Hydrogel CLs: Disinfectants Hydrogel CLs: Disinfectants

Current practice includes the following:
• Multi-purpose solution (MPS), multi-purpose disinfecting solution
(MPDS), or one-bottle system (OBS) containing one or both of the
following:
– PHX/PAPB/PHMB
– polyquaternium-1 (PQ-1)
– Alexidine dihydrochloride PolyQuaternium-1

MyristAmidoPropyl Dimethyl amine

Hydrogel CLs: Disinfectants Hydrogel CLs: Disinfectants

Biguanide
Disinfectant formulations: Some possible excipients:
• EthyleneDiamine Tetraacetic Acid (EDTA) (disinfectant enhancer,
Biguanide
Ca++ chelating agent, & water softener)
• Buffer system (phosphate, borate, or citrate-based)
Polymeric biguanide • pH adjusting agents (usually HCl & NaOH)
• Osmolality adjusting agent (often NaCl)
• Boric acid ( antimicrobial activity   concentration of
Biguanide antimicrobial required ) (Tonge et al., 2001)

• Ocular lubricant, e.g. HPMC (a viscous, cushioning agent)

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Hydrogel CLs: Storage Solutions Protein Removers

Enzymes used include:
Hydrogel lens storage by wearers is a challenge: • Papain: proteolytic, from paw paw/papaya (Carica papaya)
• Subtilisin A or B: proteolytic from Bacillus subtilis a bacterium, a serine protease (severs
• Maintaining disinfected state peptide bonds in proteins)

– CLs must remain sealed
– solution must be replaced regularly unless unneutralized
peroxide used (requires less frequent replacement)
– which solution is best?
• Full disinfection cycle needed before next wear
• Pronase: mixture of proteinases that are mucolytic (targeting mucins), derived from
non-animal source
• Amylase: enzyme that breaks down polysaccharides into sugars. Can be plant, animal,
or bacterial
• Lipase (subclass of esterases): breaks down fats & oils, can be from animal, plant, fungi,
or bacteria

• need to know in advance

Pancreatin (or pancrelipase) has been used in a contact lens protein remover & is a mixture of an amylase,
• Difficulty monitoring lens age & number of wears a lipase, & a protease. As it was a porcine product, it was unacceptable to some because of religious
beliefs or vegan preferences
– when should CLs be replaced?

Hydrogel CLs: Long-Term Storage In-Eye Products

Purpose of in-eye products:
Arguably, hydrogel lenses best stored in un-neutralized optical- • Alleviate discomfort from:
grade hydrogen peroxide. Issues include: – dry eye (or low RH environments)
– poorly wetting CLs
• Most wearers do not use/have peroxide system – noxious atmosphere
• Although stable, peroxide must still be replaced periodically (probably – ingression of foreign matter or foreign bodies
every 3-6 months) – end of day ‘dryness’ sensation & CL awareness
– tired and/or sensitive eyes
• Peroxide cannot be left in sealed lens case because slow decomposition
• Rehydrate CLs in situ
still occurs. A ruptured case releases peroxide & gives contaminants access
• Flush loose CL contaminants in situ
to CLs
•  lens deposition rate
• Solution must be neutralized before wear resumes •  friction between CL & lids as lens deposition  with lens use
– need to know when in advance • Cushion lens on the eye (viscous formulation assumed)
• The alternative, CL replacement, should be encouraged if possible •  tear protein denaturation

Hydrogel CLs: Short-Term Storage In-Eye Products

When short-term storage required, e.g. 2 wk - 2 mth, wearer should
clean CLs thoroughly & store in fresh solution as normal (compliant?).
The storage solution should be changed weekly for the duration
If peroxide normally used then either catalytic disc or neutralizing tablet
(depending on system) should be withheld until wear resumes.
Complete neutralization must occur before CLs inserted – requires
forward planning
Normal, full, 1-step peroxide cycle is unsuitable for storage because
CLs reside in ‘unpreserved saline’
In-eye products subject to greatest number of constraints including:
• Must be compatible & safe to use in-eye
• Must be sterile & remain so until after expiry date
• Must be isotonic approximately
• Must have compatible pH (6.6 – 7.8) (Harris et al., 1988)
• Must have an adequate shelf life
• Once opened, must retain sterility until
after the ‘Discard After’ date
• Must be non-irritating
• Must affect vision minimally (little effect on tearfilm stability)
• Must remain in contact with eye long enough to be effective

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In-Eye Products Silicone Hydrogel CLs

Formulation of in-eye products (continued):
• If a bioadhesive/mucoadhesive used:
– PVA
– Hyaluronic Acid (HA) (or hyaluronan, sodium hyaluronate)
– Carbomer (poly[acrylic acid]) Care & Maintenance
– HPMC
– Sodium alginate of
Alternative names used for in-eye products (in a CL context):
• Comfort drops
• Re-wetting drops, Wetting drops, Moisturizing drops
SiHy CLs
• Conditioning or Preconditioning drops
• Lubricating drops
In-eye products are not a panacea for symptomatic eyes. The root cause
of complaints should be investigated thoroughly first

Combination Products: SiHy CLs: Different or the Same?

MPSs/OBSs
• In era of convenience & ‘time-poor’ wearers (arbitrarily
1980 –), it was inevitable that LCPs & systems that were
more convenient & time saving would appear
• Most obvious was to combine functions, e.g. rinsing &
disinfection or disinfection & wetting (i.e. 1-step peroxides
& multi-purpose solutions [MPSs])
• Ultimately, this led to all functions, i.e. cleaning, rinsing, &
disinfecting, being incorporated in one product, i.e. a One
Bottle System (OBS), by the inclusion of surfactants,
wetting agents, etc.
– OBSs may be either peroxide, or PHX
and/or PQ-1-based
• When SiHy CLs introduced (1998), their manufacturers
simply recommended their own, existing hydrogel MPSs
• Later, much later than one would expect, it became
apparent that not all MPSs were ideal for SiHy CLs
• Structurally, SiHy CLs more complex than conventional Hy
CLs because they incorporate (after Carnt et al., 2007):
– Hydrophobic pDMS (poly Dimethyl siloxane)
– Fluorine species (some materials)
– Chemical entities and/or surface treatments to  lens wettability
• Therefore LCPs likely to interact differently with SiHy CLs
than with conventional Hy CLs

Combination Products:
SiHy CLs: Lens Deposition
The Current Situation
Currently, lens care market dominated by MPSs Generally, hydrogels have issues with lysozyme
Hy (protein) deposits while SiHy lenses have issues
• Peroxide systems  market share (usually <30%) & viewed as ‘problem- with lipids, especially oleic acid & its esters
solvers’ for cases of solution-induced sensitivity/staining (SICS)

– some see peroxides as more ‘complex’ SiHy

– some see 1-step peroxide as having  efficacy SiHy

SiHy

– peroxide seldom used to  adverse reactions from

SiHy
the outset
Jones & Senchyna, 2003
• Frequently, but erroneously, low complication rates with modern LCPs
attributed to the LCPs. Accolades should be conferred on the eyes’ Hy & SiHy CLs ‘absorb lipids relatively quickly (i.e., Hy
within the first day)’
abilities to look after themselves (Pucker et al., 2010B)

9

SiHy CLs: Fundamental Differences
Jones (2006) offered the following as the fundamental
differences between SiHy & Hy CLs:
• Different surface properties
• Preservative uptake behaviour
• Preservative release behaviour
Requirements for SiHy CL care include (after Jones, 2006):
• Remove deposits adequately
• Rewet & ‘condition’ lens surfaces
• Contain no components that adsorb preferentially
SiHy CLs: Lens Cleaners
• Currently, few CL cleaners formulated specifically for
SiHy CLs available
• If cleaning (& rinsing subsequently) undertaken,
usually MPS/ MPDS is used
• Conventional hydrogel cleaners can be used
• Case could be made for using alcohol-containing CL
cleaner for lipid deposit-prone SiHy CLs
– only Miraflow® (relaunched privately, late 2014) & clones
remain
SiHy CLs: Disinfecting Solutions
Currently, there are several disinfecting solutions formulated specifically for SiHy
CLs
– some MPSs reformulated once corneal staining with some
combinations of LCP & SiHy CLs confirmed (see next: Staining
Grids)
– however, MPS-associated staining was not the only issue
identified. Earlier, an incompatibility between a 1-step peroxide
(UltraCare®) & balafilcon A due to lens parameter alterations, was
reported by Jones & Dumbleton (2002)
– furthermore, polymeric antimicrobials associate with hydrophobic
domains within Hy CLs (esp. if vinyl pyrrolidone present), as do
some SiHY CLs, e.g. balafilcon A CLs) (Tonge et al., 2001)
• worse if CLs replaced infrequently, and...
• lipid accumulation exacerbates the problem
3/24/2018
SiHy CLs: Solution Incompatibilities
• In the pre-SiHy CL era, Jones et al. (1997) reported corneal staining when Group II
Hy CLs containing vinyl pyrrolidone where cared for with PHX-based LCPs
– later, using balafilcon A SiHy CLs with either a PHX or a PQ-1-
based MPS, Jones et al. (2002) observed significant, asymptomatic
corneal staining in 37% of PHX users & 2% of PQ-1 users. Similar
results were also reported by Epstein (2002)
• Importantly, the correlation between wearer symptoms & corneal staining is either
poor or absent (bandage lens effect?)
(Begley et al., 1994)
SiHy CLs: Staining Grids
• The first staining grid was by Andrasko
http://www.staininggrid.com/grid.aspx
– showed matrix of specific hydrogel & SiHy CLs (Y-axis) vs. LCPs
(X-axis)
– each cell gave a Corneal Staining Area (%) (this is controversial
because ‘staining area’ in the Staining Grid context is probably not what one would
expect – see next slide)
– confirmed that the peroxide care system used (catalytic disc
neutralization) resulted in numerically lower (but statistically &
clinically insignificantly different) staining than from unit-dose
unpreserved saline
– some combinations of SiHy CLs & MPSs resulted in more, or
much more corneal staining
SiHy CLs: What Do Staining Grids
Show
They show that:
• Not all CLs & LCPs combinations perform similarly
• Some LCPs used on SiHy CLs generally, result in more Solution-
Induced Corneal Staining (SICS)
– peroxide & unpreserved saline have similar (& low) staining
levels
• The variability in the results, even for particular CLs, suggests that the main
LCP antimicrobial is not necessarily the source of the corneal changes
– this points to differences in formulations, or...
– effects attributable to other components (excipients), or...
– effects attributable to combinations of excipients
– other, unknown or poorly understood effects
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SiHy CLs: Significance of SICS SiHy CLs: SICS - LCP Considerations

Why is SICS important?
• The risk of corneal inflammation is 3X (Carnt et al., 2007)
•  wearer comfort (Diec et al., 2012)
• SICS exhibitors showed poorer CL surface characteristics
– surface wettability may affect the corneal erosion incidence (Dumbleton, 2003)
• SICS may be associated, at least partially, with type & amount of CL surface
deposition (Willcox et al., 2007)
• While SICS may disappear by day end (epithelial repair), its peak at  2 hours
after insertion is indicative of an undesirable corneal change
• While PHX per se may not be the cause of some cases of SICS, Andrasko has
shown that a solution’s PHX concentration can affect the level of SICS
proportionally (see http://www.staininggrid.com/blog.aspx)
Willcox et al. (2010) reported: LCPs can influence corneal staining & comfort
responses during CL wear. Postulated: associated with release of ‘materials’
soaked into the CLs or changes to the lens surface composition
Imayasu et al. (2010) demonstrated: MPSs containing boric acid (an excipient)
affected adversely (downregulated) corneal cell, membrane-associated mucins
(that protect epithelium from microbial invasion)
Tanti et al. (2011) demonstrated:  cytotoxicity in vitro with borate-based MPSs,
toxicity also affected by CL type
Petersen et al. (2010) showed: corneal staining @ 2 hours wear of balafilcon A
CLs cared for in PHX-based solution, could be  significantly by the inclusion of
rub & rinse step before overnight soaking of CLs

SiHy CLs: SICS - LCP Considerations SiHy CLs: SiHy CLs vs Hydrogels
LCP considerations include (after Carnt et al., 2007) : • Jones et al. (2004) concluded: SiHy CLs  corneal staining different
– Type & molecular size of antimicrobial agent(s) from that by Hy CLs
– Interactions of the lens material & surfaces with solutions:
• Henriques et al. (2005) & Kodjikian et al. (2008) showed: in vitro
− buffers
bacterial & acanthamoebal adhesion to SiHy CLs can be > to
− chelating agents
conventional Hy CLs
− surfactants
− molality-adjusting agents • Beattie et al. (2003A) reported: up to 15X  attachment of
− pH-adjusting agents
Acanthamoeba castellanii trophozoites to SiHy CLs than to Hy CLs
– Ability of CL to act as reservoir of chemicals – attachment unaffected by lens wear & biofilm
formation (Beattie et al., 2003B)
To some extent these considerations also apply to the simpler hydrogel CLs
• However, Tomlinson (2002) reported: SiHy CL wearers were at no
Importantly, at insertion, a CL soaked in MPS is a pulse-dose application of MPS. The greater risk of acanthamoeba keratitis than conventional CL wearers
concentration of MPS diminishes rapidly over time (tear turnover-dependent). It seems
that its effects do not diminish as rapidly

SiHy CLs: SICS - LCP

SiHy CLs: Disinfectants
Considerations
SiHy CLs (& conventional hydrogels) are disinfected using solutions based on one of the following:
Gorbet et al. (2010) showed: SiHy CL surface treatments, especially balafilcon A • Hydrogen peroxide (H2O2)
CLs, can influence the effect that MPSs have on human corneal epithelial cells in • A polihexanide (PHX):
vitro. Balafilcon A CLs can bind MPSs tightly thereby  release of MPS – PAPB (PolyAminoPropyl Biguanide)

subsequently – PHMB (PolyHexaMethylene Biguanide)

– alexidine

• Polyquaternium 1 (PQ-1)
Compared with peroxide & PHX-based care systems, Diec et al. (2010) found:
• A combination of PQ-1 & MAPD
Polyquad-based LCPs on SiHy CLs :
• A combination of a PHX & PQ-1
•  first-event incidence of significant inflammatory events – currently: PHMB & PQ-1 OR alexidine & PQ-1

•  rate of SICS • Sodium chlorite (NaClO2) & H2O2 (trace amount [100 ppm] as stabilizer)

•  ease of lens handling – basically, ClO2  ClO2–

ClO2 = chlorine dioxide & ClO2– = chlorite ion
•  lens comfort – NaClO2 Na+ +Acidic 2  ClO2 (an unstable but effective disinfectant)
microbial
– components
ClO

– 4NaClO2  2NaCl + O2 + 2NaClO3

NaClO3 = sodium chlorate
Light

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SiHy CLs: MPS Formulation

Considerations
MPS/MPDS formulation considerations when targeting SiHy CLs
include:
• Potential to bind to CL material components, esp. pDMS & NVP
– binding, affects release subsequently
– buffer system used
• Effects on surface properties &/or wettability
• Comparing 1-step H2O2 systems with a PQ-1-based MPDS, Kier et al.
(2010) reported longer wearer comfort with H2O2

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