2. Contact Lens Care Products: Properties & Performance Lecture 5L3 Version: 2012-May-10 1 Published in Australia by The International Association of Contact Lens Educators SecondEdition 2011

3. The IACLE Contact Lens Course (all formats) is the sole property of the International Association of Contact Lens Educators (IACLE) and is protected, without limitations, by copyright. By accessing this material, you agree to the following terms and conditions: You may only access and use the IACLE Contact Lens Course for personal or educational purposes. Any dissemination or sale of the IACLE Contact Lens Course, either in whole or in part, or use of the materials for other than educational and personal purposes, is strictly prohibited without the express written consent of IACLE. Except as declared below, you may not reproduce, republish, post, transmit, or distribute any material included in the IACLE Contact Lens Course. You may print materials for personal or educational purposes only. All copyright information, including the IACLE logo, must remain on the material. Appropriate reference must be provided to any use of the content of the IACLE Contact Lens Course, including text, images, &/or illustrations. COPYRIGHT NOTICE

4. SPONSORS Development and delivery of contact lens education by IACLE is supported through educational grants and in-kind contributions Major In-Kind Supporters Industry Supporters

5. Published in Australia by The International Association of Contact Lens Educators Revised Edition 2011 The International Association of Contact Lens Educators 2000-2011 All rights reserved. No part of this publication may be reproduced, stored in a retrieval system, or transmitted, in any form or by any means, without the prior permission, in writing, of: The International Association of Contact Lens Educators IACLE Secretariat, PO Box 656 KENSINGTON NSW 2033 Australia Email: iacle@iacle.org

6. 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

7. Clean CLs Prevent/minimize CL deposits Maintain CL hydration & wettability to   comfort &  vision Disinfect CLs to prevent ocular infection & inflammation CARE & MAINTENANCE PURPOSES

8. COMPLICATIONS DEPOSITS   irritation &  comfort  visual acuity  CL life  bacterial binding   potential for infection  incidence of CLPC/GPC

9. COMPLIANCE vs. NON-COMPLIANCE Simple system & appropriate instructions  better compliance Complicated systems can lead to: -confusion -non-compliance -complications  lens wear

10. COMPLIANCE INDEX CLINICAL ASPECTS Good lens care compliance Poor lens care compliance 100 0 80 60 40 20 Epithelial Staining Lens Deposits Symptoms COMPLIANCE [%] 50 10 50 20 40 5 Collins & Carney (1986)

11. CARE & MAINTENANCE PROCESSES Cleaning Rinsing Disinfection Periodic protein removal Re-wetting/lubricating Care & replacement of CL case ESSENTIAL STEPS ADDITIONAL STEPS

12. LENS SPOILAGE

13. 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

14. 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 DETAILS ON BUFFERS/pH CLICK FOR MORE DETAILS ON OSMOLALITY CLICK FOR MORE ON ALCOHOLS

15. 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

16. 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

17. 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

18. CL CLEANERS SURFACE TENSION (ST) Surfactants disrupt surface forces thereby lowering ST CLICK FOR MORE DETAILS ON ST

19. 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

20. 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™)

21. SURFACTANT CLEANERS TYPES Daily cleaners Periodic cleaners

22. 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

23. EXCIPIENTS GENERAL Solution excipients play ‘supporting’ rôle. Such rôles include: –↕ solution pH, tonicity, or viscosity –  efficacy of main (active) components

24. 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

25. 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)

26. 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

27. 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

28. 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

29. EDTA CHEMISTRY

30. 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

31. 500 mL SALINE STUDY WIDE-MOUTHED BOTTLES Sweeney et al., 1992 100 50 100 0 20 40 60 80 100 Week 1Week 2Week 3Week 4 TestControl % CONTAMINATED WEEKS OF USE

32. 500 mL SALINE STUDY JET or SMALL APERTURE BOTTLES Sweeney et al., 1992 % CONTAMINATED WEEKS OF USE

33. 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.

34. WHY IS DISINFECTION REQUIRED? CLs can: Inhibit tear film’s washing action Introduce micro-organisms Compromise the epithelium’s barrier function

35. DISINFECTION: FUNCTION Disinfection is central to  number of potentially harmful micro-organisms on CLs

36. 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)

37. 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 wearersStill used on some trial CLs

38. 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)

39. 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

40. DISINFECTION/PRESERVATIVES: KNOWN OCULAR IRRITANTS Thimerosal (a Hg-based compound) Chlorhexidine (a biguanide) Sorbic Acid (now uncommon)

41. 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)

42. 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?)

43. 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

44. CHEMICAL DISINFECTANTS : POLYMERIC The basis of all current MPSs The polihexanides (PHX), a generic term for: 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 CLICK FOR MORE ON PHXs

45. 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 test- panel 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

46. 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 micro- organisms,  task of disinfectant subsequently Compliance more important  margin for error due to  (deliberate) solution antimicrobial efficacy

47. ANTIBACTERIAL EFFICACY * Heat (80°C, 10 min) 3% H 2 O 2 (2-Step) (10 min) (unneutralized) 3% H 2 O 2 (1-Step) (6 hrs) (disc neutralization) 0.002% Thimerosal (4 hrs) 0.00005% PHMB (4 hrs) 0.001% PQ-1 (4 hrs) after Lowe et al., 1992, Reinhardt et al., 1990 * within MRDT MRDTs #

48. ANTIFUNGAL EFFICACY * Heat (80°C, 10 min) 3% H 2 O 2 (2-Step) (10 min) 0.002% Thimerosal (4 hrs) after Lowe et al., 1992, Reinhardt et al., 1990 * within MRDT 0.00005% PHMB (4 hrs) 0.001% PQ-1 (4 hrs) 3% H 2 O 2 (1-Step) (6 hrs) GOOD POOR

49. ANTIAMOEBIC EFFICACY* Heat (80°C, 10 min) 3% H 2 O 2 (2-Step) (4 hrs) 0.002% Thimerosal (6 hrs) after Davies et al., 1990 * within MRDT 0.00005% PHMB (4 hrs) 0.001% PQ-1 (4 hrs) 3% H 2 O 2 (1-Step) (6 hrs) GOOD POOR

50. 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 

51. 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

52. 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

53. 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

54. 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 para- chlorophenyl 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

55. ALEXIDINE (ALEX) Ethyl groupHexyl group para-Chlorophenyl group CLICK FOR CURRENT DISINFECTANTS/MPSs Biguanide group

56. HYDROGEN PEROXIDE (H 2 O 2 )  free oxygen radicals that are very reactive & bind quickly to many microbial cell components 2H 2 O 2 2H 2 O + O 2 Hydrogen peroxide solutions require a stabilizer in the interests of long-term stability CLICK FOR MORE ON H2O2 & STABILIZERS

57. HYDROGEN PEROXIDE (H 2 O 2 ) A non-selective antimicrobial agent Neutralization: 2-step systems –serial dilution (historic, imperfect, [H 2 O 2 ] ≠ 0 ) –pH shifting (historic, 1 st generation, NaHCO 3 ) –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

58. HYDROGEN PEROXIDE (H 2 O 2 ) Minimum 3 hours in 3% H 2 O 2 recommended, overnight preferred (6-9 hours) Bacteria10-15 min Fungi60 min Acanthamoeba sp.3 - 6 hours Suitable for all lens types (including GP CLs) 2-Step Systems

59. HYDROGEN PEROXIDE (H 2 O 2 ) 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 2-Step Systems: ADVANTAGES

60. HYDROGEN PEROXIDE (H 2 O 2 ) 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 2-Step Systems: DISADVANTAGES

61. HYDROGEN PEROXIDE (H 2 O 2 ) Longer neutralization/equilibration times required Vented lens case not required –simpler & less expensive No ‘activity’, e.g. bubbling, visible –no visible confirmation of neutralization STOICHIOMETRIC NEUTRALIZATION

62. HYDROGEN PEROXIDE (H 2 O 2 ) 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 CATALYTIC NEUTRALIZATION

63. HYDROGEN PEROXIDE (H 2 O 2 ) Convenient Preservative-free (disc or tablet neutralization) Concurrent protein removal possible –peroxide-compatible product required such products are available off-the-shelf 1-Step System: ADVANTAGES

64. HYDROGEN PEROXIDE (H 2 O 2 ) No control over disinfection phase [H 2 O 2 ]  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) 1-Step System : DISADVANTAGES

65. HYDROGEN PEROXIDE (H 2 O 2 ) [H 2 O 2 ] & pH changes during a peroxide DISINFECTION cycle

66. HYDROGEN PEROXIDE (H 2 O 2 ) 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

67. HYDROGEN PEROXIDE (H 2 O 2 ) 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

68. HYDROGEN PEROXIDE (H 2 O 2 ) Caution required 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 glutathione peroxidase (corneal epithelium [medium concentrations]) superoxide dismutase (corneal epithelium [medium concentrations]) catalase: –(conjunctival epithelium [heavy concentrations]) –(corneal epithelium [medium concentrations]) Chalmers et al., 1989 Located in:Can deal with:

69. HYDROGEN PEROXIDE (H 2 O 2 ) OCULAR TOLERANCE Anterior eye ‘detection’ (discomfort) thresholds for H 2 O 2 If a solution contains H 2 O 2 (a pulse-dose), 812 ppm (SD ±312) will be detected with 95% probability If a 55% water hydrogel CL has residual H 2 O 2 (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 [H 2 O 2 ] but to soaking solution/lens pH (too low) (Janoff, 1990) Chalmers & McNally, 1988, Janoff, 1990, McNally, 1990 CLICK FOR A LIST OF CURRENT PEROXIDE SYSTEMS

70. LESS CONVENTIONAL DISINFECTION METHODS Sodium chlorite  Chlorine dioxide UV-C irradiation (induces DNA cross-linking in micro- organisms 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) CLICK FOR MORE ON ClO 2

71. 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)

72. 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

73. PROTEIN REMOVAL Effective protein deposit removal is essential in all CLs except very frequent disposables (<14 – <30 days – patient- dependent) 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

74. 5L1-73 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

75. PROTEIN REMOVAL Done regularly, after daily cleaning & rinsing steps Can be done BEFORE disinfection, or done DURING disinfection (with H 2 O 2 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

76. 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)

77. 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)

78. 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

79. 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

80. RE-WETTING & LUBRICATING DROPS Considerations: 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 (after Tonge et al., 2001)

81. 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

82. 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

83. 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

84. 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

85. 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

86. 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)

87. 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

88. 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

89. 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)

90. 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

91. 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

92. LENS STORAGE CASE CARE Replacement cases

93. 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

94. 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

95. CARE & MAINTENANCE: SUMMARY CRADLECRADLE CRADLECRADLE lean inse nd isinfect enses very time OR.....

96. CARE & MAINTENANCE: SUMMARY continued... If in doubt, throw them out!

97. IACLE INDUSTRY SPONSORS

98. 5L1-97

99. 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

100. 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)

101. 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 1- step + 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)

102. SOLUTION PROPERTIES ACIDS & BASES ACID: –Brønsted-Lowry (1923) definition: PROTON donor –Lewis (1923) definition: ELECTRON PAIR acceptor 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 The Lewis definition is applicable more generally RETURN TO LECTURE

103. 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

104. 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/m 3 @ +3.984° C at 1 atmosphere of pressure). This suggests that 1 L is not 1,000 cm 3 but 1,000.028 cm 3, i.e. 1 mL is fractionally smaller than 1 cm 3. Solution osmolality =  the osmotic pressures of each of the solutes present

105. 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

106. SOLUTION PROPERTIES SURFACE TENSION (ST) Surface molecules All other molecules Nominal surface

107. SOLUTION PROPERTIES SURFACE TENSION (ST) 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 Unlike ‘inner’ molecules, surface molecules have no fellow molecules to ‘reach out to’. Their interaction with adjacent materials is material (both) dependent

108. SOLUTION PROPERTIES WETTING (A WETS B) A B Surface of A Surface of B ST A ST B ST A ST B ST Lower ST Higher (CL) (Cornea) (Tears) (Wetting Soln.) (Cleaner) (MPS) Lower ST Higher ST

109. 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 ST Cornea 67.5 to 72 mN/m (Glasgow et al., 1999) ST Tears 42 to 71.5 mN/m (Zhao & Wollmer, 1998, Nagyová & Tiffany, 1999) ST PMMA 32 to 49 mN/m (Rankin & Trager, 1970, Goudeau et al., 2000, Zagari et al., 2004) ST Water 72.8 mN/m at 20°C (sometimes 72.8 dynes/cm – not SI units) ST LCPs 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 ST PTFE ( 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

110. 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

111. 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

112. 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

113. 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 micro- organisms 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

114. 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

115. PRESERVATIVES BAK Benzalkonium chloride (BAK) Quaternary ammonium compound Mixture of alkyldimethylbenzylammonium chlorides (ADBACs) of various even-numbered alkyl (-CH 2 -) 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

116. DISINFECTANTS IUPAC Name: Dihydrogen Dioxide 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)

117. DISINFECTANTS PEROXIDE STABILIZER DTPMP or diethylenetriamine penta(methylene phosphonic acid) DTPMP: used as hydrogen peroxide stabilizer RETURN TO LECTURE

118. DISINFECTANTS BIGUANIDES

119. DISINFECTANTS BIGUANIDES continued... RETURN TO LECTURE

120. PolyQuaternium-1 MyristAmidoPropyl Dimethyl amine DISINFECTANTS POLYQUATERNIUM-1 RETURN TO LECTURE

121. DISINFECTANTS ALCOHOLS RETURN TO LECTURE Modes of Action:

122. DISINFECTANTS OTHERS RETURN TO LECTURE Light Acidic microbial components Sodium chlorite (NaClO 2 ) & H 2 O 2 (trace amount [100 ppm] as stabilizer) –basically, ClO 2  ClO 2 – –NaClO 2  Na +  ClO 2 –  ClO 2 (an unstable but effective disinfectant) –4NaClO 2  2NaCl +  O 2 + 2NaClO 3 ClO 2 = chlorine dioxide & ClO 2 – = chlorite ion NaClO 2 = sodium chlorite NaClO 3 = sodium chlorate

123. DISINFECTANTS EXCIPIENTS: EDTAs EthyleneDiamine Tetraacetic Acid or Edetic Acid Disodium EDTA or Edetate disodium or Edetate sodium (sodium salt of EDTA) Only differences RETURN TO LECTURE

124. CAS REGISTRY NUMBERS RETURN TO LECTURE 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.http://www.cas.org/ Few manufacturers are forthcoming with the CAS #s of their LCP ingredients

125. 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

126. SURFACTANT CLEANERS GP (DAILY) Cleaners for GP CLS Alcon OPTI-FREE  SupraClens  Alcon Opti-Clean  II Daily Cleaner Alcon OPTI-FREE  Daily Cleaner Alcon Unique  pH (limited channels) Alcon POLYCLENS ® II Daily Cleaner AMO AMO Total Care  Cleaner AVIZOR GP Cleaner AVIZOR Cleaning Drops Boston ® Cleaner Boston ® Advance  Lens Cleaner Boston ® Cleaner - Original Formula contopharma i-clean! (Miraflow  clone?) contopharma GPHCL Cleaner CIBA Vision Miraflow  Cleaner (avail.?) CIBA Vision Miraflow  Extra Strength Cleaner DISOP Durasol Cleaner N.B. Some products listed are identical but are marketed under different names in different international markets Some products appear in both GP and Hy & SiHy lists, i.e. they are ‘universal’ & are suitable for use on GP, Hy, & SiHy CLs Cleaners for GP CLS EYEYE Crystal Cleaner Lobob ® Optimum Extra Strength Cleaner Lobob ® Sterile Cleaning Solution Menicon Spray & Clean Optikem Intn’l Sereine ® Contact Lens Cleaner Piiloset DAILY CLEANER Purahard Cleaner Sauflon delta cleaner

127. SURFACTANT CLEANERS Hy & SiHy CLs (DAILY) Cleaners for Hy & SiHy CLS 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 N.B. Some products listed are identical but are marketed under different names in different international markets Some products appear in both GP and Hy & SiHy lists, i.e. they are ‘universal’ & are suitable for use on GP, Hy, & SiHy CLs

128. SURFACTANT CLEANERS CURRENT MARKET (PERIODIC) Cleaners for GP CLS Professional/Laboratory use ONLY Cleaners for Hy & SiHy CLS Boston ® Laboratory Lens Cleaner MeniCare Progent MeniLab Cleaner AVIZOR Lipid Clean for SiHy CLs RETURN TO LECTURE

129. 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

130. 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

131. 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

132. 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

133. 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

134. 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

135. 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

136. 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

137. 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

138. 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

139. 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

140. 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

141. 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

142. 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

143. 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

144. 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

145. 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

146. 5L3 End of appendices

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148. 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. 3 rd 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.

149. 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. 2 nd 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.

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