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5/26/2011 Prescribing Contact Lens Solutions: Making Informed Decisions William D. Townsend, OD. FAAO Advanced Eye Care Canyon, TX Adjunct Professor, UHCO Houston, TX [email protected] • As a paid speaker I have been sponsored by several companies including Alcon, Allergan, CIBA, Cooper Vision, Odyssey Medical, Medical and VSP • I am not a consultant to nor an employee of any pharmaceutical or industry company. • Any product superiority mentioned during this presentation will be supported by scientific studies and white papers. 2010-Contact Lens Dynamics in US Market Financial Disclosure William D. Townsend,O.D., F.A.A.O. • William D. Townsend OD has received honorarium from Alcon Allergan, Alcon, Allergan CIBA, CIBA Cooper Vision, Odyssey Medical, and VSP. He is not on the board of any ophthalmic drug or contact company Dissatisfied Blissful (Tolerant Sufferer) Borderline SCL wearers New wearers 3.8 million/year Base of 30.2 million soft CL wearers (54% > 35 yrs old) Post-Refractive Lens Wear 10% of Procedures 80 K Other reasons Lost to CL wear 3.0 million (10%) per year 3.0 million drop out of lens wear 1.6 M undergo refractive procedures 800 K are CL wearers Sources: Nielsen Household Panel, IPSOS NPD Tracker Consumer Surveys, Alcon estimates Why do patients drop out of CL’s? Reason Discomfort Dry eye symptoms Red eye symptoms Insertion/removal Poor vision Advised by doctor Pregnancy Other (cost, presbyopia, photophobia, no answer) Soft 40% 10% 5% 3% 3% 3% 4% 23% RGP 58% 11% 3% 3% 7% 3% 3% 11% When patients present with contact lens-associated discomfort……. • Change the fit • Change the material- (wetter) • Change Ch the th brand b d • Add re-wetting drops • Try punctal plugs • Evaluate for solution-related complications, compatibility 1 5/26/2011 Why patients drop out • Vision ¾ Presbyopia inadequately corrected ¾ Dryness ¾ Poor lens surface quality • Convenience-should not be an issue • Comfort #1 ¾ Poor fit ¾ Dryness (actual or perceived) • Loss of surface conditioning • Coated lens surfaces ¾ Solution allergy ¾ Solution toxicity ¾ Solution-related Milestones in CL Solutions, Materials • Soft lenses introduced- 1971 Bausch & Lomb • Heat disinfection- 1971 • Thimerosol- 1977 Flexsol & Flexcare BP/Alcon ¾High rate of allergy • Chlorhexidine- SoftMate Disinfecting Solution BH • New generation solutions solutions- 1980 1980’ss lower toxicity • Advent of silicone hydrogel materialsEurope in 1999 and the US in 2001. • Old solutions not necessarily compatible with new materials • New solutions may not be compatible with old materials 2010: Great expectations from multipurpose contact lens solutions? • Kill bacteria, viruses, fungi, amoeba • No rubbing required p y with tear p pH, osmolarity y • Compatibility • Compatibility with all CL materials • Stability over life of the container • Wet and condition the lens surface • Enhance comfort of CL wear • Affordability Our goal today is………. • Identify solutions problems unique to hydrogel lens “groups” • Identify solutions problems unique to silicone hydrogel lenses • Review known adverse interactions between lens materials and solutions • Empower you with a scheme for evaluating future CL solutions and drops • Lower the rate of CL dropouts your practice Crucial Issues in Choosing CL Solutions- What Patients Want • Comfort • Convenience • Cost • Confidence Compliance ¾What did the doctor or tech tell them? Crucial Issues in Prescribing CL Solutions- What Doctors Want • Eye-Solution compatibility • Lens Lens-Solution Solution compatibility • Lens-Surface wettability HAPPY PATIENTS who continue to wear contacts and support your practice 2 5/26/2011 Factors that influence informed solution prescribing decisions Improving Lens Comfort Are There Differences Between MPS Products? COMFORT Influenced by: Wettability + Cleanliness + Compatibility Lasting surface wettability Absence of pathogens, debris and protein Dynamic wettability test over time Disinfection testing Lysozyme removal • Lens material: water content, ionic vs non-ionic, silicone hydrogel vs hydrogel • Use: daily vs. extended vs. flexible wear • Protein coating/uptake characteristics ¾ Hydrogel d l vs. silicone ili h hydrogel d l ¾ Location, depth, and denaturing Minimize ocular stress • Patient history ¾ Infection, keratitis ¾ Allergy ¾ GPC ¾ Other Corneal staining • Physical exam Making informed decisions: we do it all the time! • • • • 48 yo male with large internal hordeolum HIV positive with T-cell count of 120 No prescription drug coverage w/ insurance What is your decision making process? ¾ I need a bactericidal drug. drug ¾ I need a drug w/ good gram+ coverage. ¾ I need a drug w/low incidence of resistance. ¾ I need a generic drug to keep cost down. • Your solution is to prescribe……. Augmentin 875 mg Q 12 hours! But how do we make informed decisions in prescribing CL solutions? Methylcellulose Hydranate Potassium chloride Polyquad Tetronic 1304 Group 2 Lenses PHMB Pluronic Citrate Edetate disodium Sodium borate Povidone Tetronic 1107 Dymed Poloxamine Alexidine Hydrogel Lens Groups • Created in 1986 for solution companies • Categorized “for purposes of evaluating effects of accessory products on the lens materials” • Based on water content and ionic charge • “Low water"- less than 50 % water content • “High water"- all others • “Ionic"- (highly charged) materials • “Non-ionic“- (low charge) surfaces 3 5/26/2011 Contact Lens Materials Groups GROUP 1 Low Water (<50% H20) Non-ionic Polymers GROUP 2 High Water (>50% H GROUP 3 Low Water (<50% H20) GROUP 4 High Water (>50% H20) Non-ionic Polymers Ionic Polymers Ionic Polymers Cibasoft Preference CSI Gold Medalist Toric Hydrocurve II 45 Acuvue sphere Soft Mate B Acuvue toric Soflens 66 Proclear DuraSoft 2 Focus monthly Focus Toric Soflens Focus Dalies •Focus Night/ Day •Accuvue Oasys •Acuvue Advance Sariri R. Protein interaction with hydrogel contact lenses. Journal of Applied Biomaterials & Biomechanics 2004; 2: 1-19 Biomedics Toric Biomedics 55 •PureVision Material does make a difference! •Silicone hydrogels Hydrogel vs. Silicone Hydrogel Lens • O2 Permeability ¾ Increased H2O content HG = increased O2 ¾ Increased H2O content SiHG = decreased O2 • Lipid coating ¾ Rare in hydrogels ¾ Very y common in silicone hydrogelsy g must rub! • Protein coating ¾ Hydrogels- minimal denaturing ¾ Silicone hydrogels- extensive denaturing • Matrix absorption of preservative a factor? ¾ Hydrogel- yes ¾ Silicone hydrogel- no Early Preservatives • Thimerosal ¾ Mercurial compounds ¾ Allergies • Benzalkonium Chloride (BAK) ¾ Cationic detergent ¾ Affects lens wettability & tear film stability ¾ Concentrates C t t in i lens l matrix, t i released l d later l t ¾ Causes toxic keratitis • Chlorhexidine ¾ Biguanide germicidal agent ¾ Less sensitization than thimerasol, but toxic to epithelium • Sorbic Acid – discolors lenses What goes into a CL solution? • Water (actually, really good water) • Electrolytes • Cushioning agents • Chelating agents Preservatives / Disinfectant Buffering agents Cleaning agents Wetting / Conditioning agents 21st Century Preservatives • Aldox (myristamidopropyl dimethylamine) Small MW ≈ 300 ¾ Anti-fungal activity2 ¾ Acanthamoebicidal activity ¾ Anti-bacterial activity • Alexidine Small MW≈ 500 ¾ Biguanide used in dentistry since mid ’70’s ¾ Causes cell lysis by interference with the layer phospholipid of the microorganism’ss cytoplasmic membrane microorganism • Polyhexamethylene biguanide (PHMB) Medium MW≈ 800 ¾ Biguanide class (includes chlorhexidine) ¾ Anti-microbial efficacy ¾ Cytotoxic reactions dependent on concentration • Polyquad (polyquaternium-1) Large MW ≈ 8,000 ¾ Reduced cytotoxicity ¾ Potent bactericide ¾ Large molecule reduces absorption 4 5/26/2011 Why patients (and doctors) are confused • FDA “stand alone criteria” ¾After inoculation, solution must show: • Three log units of kill for bacteria • One log g unit of kill for fungi g • MPS (not stand alone)- cleans, disinfects, rinses, and stores Product Preservative(s) Cleaning Agents Wetting Agents OPTI-FREE® EXPRESS POLYQUAD 0.001% ALDOX0.0005% Sodium citrate,AMP-95*, TETRONIC 1304 TETRONIC®† 1304 OPTI-FREE RepleniSH POLYQUAD 0.001% ALDOX 0.0005% Sodium citrate,TETRONIC 1304 w/ Tearglyde TETRONIC®† 1304 w/ Tearglyde ReNu MultiPlus* PHMB 0.0001% Hydranate, TETRONIC 1107 None Complete* PHMB0.0001% Poloxamer 237, EDTA Hydroxypropyl methylcellulose Aquify PHMB 0.0001% Poloxamer 407 Hydrolock (Dexpanthanol and Sorbitol) ¾(rubbing required) • MPDS (stand alone)- same as MPS but higher disinfectant criteria Aosept Clear Care* Biotrue Hydrogen peroxide 0.3% Pluronic* 17R4 None PHMB 0.0001% POLYQUAD 0.0001% TETRONIC 1107 TETRONIC 1107 Sodium hyaluronate ¾(no rubbing required) Potential Preservative-Lens-Eye Interactions Strategies to Reduce Ocular Exposure to Cytotoxic Substances • Preservatives may: ¾ Adsorb (attract and hold to surface minute particles of mixture or molecules of gas or liquid) ¾ Absorb (to take something in through pores on surface and into lens matrix)) ¾ Be released onto the ocular tissue possibly resulting in a potential cytotoxic response ¾ These may occur more frequently with small molecule preservatives • Prevention of above requires blockage of lens sites to prevent absorption and release Lebow K, Schachet, J Evaluation of Corneal Staining and Patient Preference With Use of Three Multi-Purpose Solutions and Two Brands of Soft Contact Lenses. Eye & Contact Lens October 2003 • Two randomized, investigator-masked, 2-month crossover studies • Study 1- 45 subjects used Opti-Free Express & C Complete l t ffor 1 month th then th crossover • Study 2- 44 subjects used Opti-Free Express and ReNu MultiPlus for 1 month then crossover • Lenses used: ¾ Accuvue 2- group 4 ¾ Soflens 66- group 2 • Use a large MW preservative or molecule with minimal ionization • Prevent lens adsorption or release of offending chemical • Provide shielding of lens using a charged molecule (ie. citrate) • Modify preservative size & charge to reduce adsorption and release OPTI-FREE EXPRESS MPDS vs. ReNu Multi-Plus Staining Worse Better p = 0.0091 p = 0.0001 Accuvue 2 p = 0.0002 p = <0.0001 p = <0.0001 p = <0.0001 SofLens 66 * Lebow KA, Schachet JL. Evaluation of corneal staining and patient preference with the use of three multi-purpose solutions and two brands of soft lenses. Eye & Contact Lens. 29(4):213-20, 2003. 5 5/26/2011 OPTI-FREE EXPRESS MPDS vs. ReNu Multi-Plus OPTI-FREE EXPRESS MPDS vs. Complete MPS Comfort Staining P = 0.04 Worse P = 0.04 p = 0.61 ns p = 0.97 ns Acuvue 2 •Lebow KA, Schachet JL. Evaluation of corneal staining and patient preference with the use of three multi•purpose solutions and two brands of soft lenses. Eye & Contact Lens. 29(4):213-20, 2003. OPTI-FREE EXPRESS MPDS vs. Complete MPS Comfort p = 0.72 ns p = 0.70 ns p = 0.49 ns p = 0.79 ns SofLens 66 * Lebow KA, Schachet JL. Evaluation of corneal staining and patient preference with the use of three multi-purpose solutions and two brands of soft lenses. Eye & Contact Lens. 29(4):213-20, 2003. Lessons to be Learned • Staining occurs with all preservatives selectively worse in 1st 6 hours of wear • Polyquad preserved solutions show less staining at 2-4 hours compared to PHMBpreserved d solutions l ti • PHMB staining is proportional to concentration if all other components in solution are the same * Lebow KA, Schachet JL. Evaluation of corneal staining and patient preference with the use of three multi-purpose solutions and two brands of soft lenses. Eye & Contact Lens. 29(4):213-20,2003. Preservatives and Anti-microbial Activity? ¾But they are not! ¾Differences in staining not explained by preservative alone Dannelly H and Waworuntu R. Effectiveness of Contact lens disinfectants after lens storage. Eye and Contact lens, March 2004 • Must kill pathogens, especially gram negative (pseudomonas) • Must kill amoebae • Must act within hours • Must have low toxicity to ocular tissue Log Reduction after 8 hours 6 5/26/2011 Dannelly H and Waworuntu R. Effectiveness of Contact lens disinfectants after lens storage. Eye and Contact lens, March 2004 FDA Guidelines • Recent recalls suggest that present standards, methods not realistic effective realistic, • Need more “real-life” strategies for evaluating contact lens solutions, drops Log Reduction after 8 hours Buffering Agents in CL Solutions • Stable lens parameters ¾Acidic pH promotes lens dehydration and steepening (tighter fit of the lens on the cornea); ) ¾Alkaline pH promotes hydration and flattening (looser fit on the cornea). • Tear pH affects cleaning efficacy of surfactants Buffers and Lysozyme Removal • 90% of tear protein is lysozyme • Borate-buffered solutions marginally remove lysozyme • Citrate-buffered solutions maximally remove lysozyme ¾Citrate molecule is negatively charged and pulls protein away from lens surface Buffering Agents in CL Solutions • As washing proceeds, the alkalinity or pH drops • Under acidic (low pH) conditions, cleaning is reduced. • Buffering agents ¾Stabilize the pH and lens shape ¾Enhance the cleaning attributes of the solution ¾May positively or negatively affect toxicity of disinfectants on the eye Cleaning & Wetting Agents • Important for removal of surface contaminants • Can positively or negatively affect surface wetability • Can be customized to increase lipophilicity and hydrophilicity 7 5/26/2011 Proteins in the Eye ethylene oxide (hydrophilic) • Every protein in our body has a function. propylene oxide (lipophilic) ¾ Lysozyme: The main protein found in tears; primarily has antimicrobial activity bridge molecule (diamine) • Proteins can be found in two states ¾ Native State: natural (folded) state ¾ Denatured State: forms deposits p which bind to the surface of the lens and cause irritation • Can be recognized by immune system as “non-self” • Can lead to development of GPC • Cleaner/conditioner can prevent binding of denatured proteins to hydrogel or silicone hydrogel lenses Pluronic Structure Tetronic Structure Tetronic Block Copolymers EW Lysozyme Deposit Curve Acuvue 2 w/ no Solutions The Tetronic® surfactants are tetrafunctional block copolymers based o on e ethylene y e e oxide o de and a d propylene oxide. They function as anti-foaming agents, wetting agents, dispersants, thickeners, and emulsifiers. (BASF literature) Days EW HPLC Assay Christianson et al Inter-Patient Variability OFX vs ReNu Multiplus Patients coat lenses differently! (3 Crossover studies combined) AV-2 DW (after Rub/Rinse & overnight soak) ReNu MoisturePlus Patient 105 Patient 101 HPLC Assay ug Lysozyme e/ lens Previous Slide Pop. Mean EW OFX Days wear Days of EW Christianson et al Christianson et al 8 5/26/2011 Hydrogel Considerations • Hydrogel lenses, particularly highwater types, attract protein • Mucin and lipid deposits are a little less problematic in hydrogels • Select a solution that minimizes hydrogel coating i with i protein i • Select a lens material that has reduced dehydration attributes ¾Proclear 62% water ¾Extreme H2O 59% water What about new solutions, old materials? Townsend, Katims, & Rosen. Investigating a NewGeneration Multi-Purpose Solution. Contact Lens Spectrum December 2005 • 30 patients in 3 diverse geographic locations • Compared OFX to ReNu MoistureLoc for staining, comfort and wearing time • Non-masked study, crossover using Accuvue 2 lenses • Evaluated at entry, 2 weeks, and exit Where are we headed with lens materials and solutions? • Silicone hydrogels gaining in market share • Increasing use as daily wear • New materials designed for compatibility with these lenses • Matched lenses materials by labels ¾B&L- Pure Vision with Renu MoistureLoc ¾B&L- Biotrue and Purevision ¾CIBA- Night & Day with AQuify Townsend, Katims, & Rosen. Investigating a NewGeneration Multi-Purpose Solution Contact Lens Spectrum December 05 • Mean staining grade for ReNu MoistureLoc was 0.97 compared with 0.52 for Opti-Free Express. • Mean staining area was 1.6 for all segments for ReNu MoistureLoc while mean staining area was 1.2 for all segments for Opti-Free Express • Optifree Express was preferred by a greater number of participants in several categories including overall comfort, keeping lenses comfortable for longer, ease of handling, better vision, and reduced sensation of dryness. Andrasko Corneal Staining Grid Lens and Solution Combinations Percentage of Average Corneal Staining Area at 2 Hours Crucial Issues in Compatibility ReNu OptiWal-Mart Complete ReNu OPTI-FREE® MoisturePlu Aquify* Unisol 4 Free® RepleniSH® MoistureLoc MultiPlus* Equate* s* * Saline EXPRESS ® MPS MPS MPDS MPS MPDS MPS MPS ® • Which lens material and solutions are compatible? • Which lens material and solutions are not compatible? • Is there a source for answering the above questions? Acuvue 2 * 1% 2% 5% 25% P PureVision Vi i * 2% 6% ‡ 7% 6% Acuvue Oasys * 2% 3% ‡ 5% 10% O2 Optix * 2% 2% ‡ 5% 7% Focus Night&Day * 2% 4% ‡ 3% 6% ‡ POLYQUAD® 1% 1% 2% 1% 73% 71% 48% 21% ‡ Testing Ongoing Testing Ongoing 24% 12% 5% 1% ‡ 41% 18% 7% ‡ 36% 16% 3% BIGUANIDES 9 5/26/2011 The “Conditioning Concept” • Lenses out of the blister pack have certain features that are lost after wear • Maintaining that “conditioned” surface probably helps patient comfort; therefore retention What Really Happens? • Bulk water loss from a hydrophilic lens is minimal regardless of intrinsic water content or lens group. • Drying occurs on the lens surface, but is much more than water loss! • Changes in lens surface wetting can be measured by wetting angle measurement. • Surface drying may be related to decreased lubricity and discomfort (Lid Wiper Epitheliopathy). August 2005 Hydrophilic versus Hydrophobic Molecular Orientation at the Contact Lens Surface HO HO CH 3 CH 3 CH 3 CH 3 O CH3 O O CH3 O O O O CH3 O O OO OH OH OO OO O CH3 OH OH OH OH Hydrophilic orientation Hydrophobic orientation Amos C. Performance of a New Multipurpose Solution Used with Silicone Hydrogels. Optician 2004 • Compared staining in Night & Day patients using ReNu MultiPlus and AQuify MPS • Both B th preserved d with ith PHMB 0.0001% 0 0001% • After one month ¾Renu group-24% showed staining ¾AQuify group- no staining • Why? Concentration of PHMB same • Formulation is the difference AQuify? • Formulated for use with Ciba’s Focus Night & Day lenses • Unique formulation allows overnight or 5-minute disinfection (RUB) • Buffering agents may have advantages over other solutions • High wetting angle when used with hydrogels and silicone hydrogels • Good staining profile AQuify • Good choice for most silicone hydrogels- especially Night & Day • HydroLock" lubricating system ¾Dexpanthenol (ProVitamin B5), a moisturizer it i ¾Sorbitol, a humectant • Unique time option ¾5 minute soak with rub ¾4 hour soak without rub • Effectively removes lipid, the “culprit” in silicone hydrogels 10 5/26/2011 Optifree RepleniSH • Specifically formulated for SiHy compatibility (also hydrogels) • Excellent wetting angles with hydrogel and SiHy • Some issues with hypersensitivity not seen in original Optifree Express Amos: Waterloo Study • Compared Clear Care with Opti-Free Express patients wearing Night & Day daily wear • After 1 month ¾0% of Clear Care had staining ¾8% of Opti-free had staining FDA Guidelines • Recent recalls suggest that present standards, methods not realistic, effective ¾ Ciba Aquify recalled November 2005 ¾ B&L MoistureLoc recalled April 2006 ¾ AMO Complete recalled May 2007 • All used biguanide-based preservatives • Need more “real-life” strategies for evaluating contact lens solutions CIBA Vision- Clear Care • One bottle peroxide-based solution • Bubbling action removes surface contaminants • Contains Pluronic 17R4 as a cleaning agent • No conditioning agent! • Very high wetting angles My opinion… • Hydrogen peroxide systems are safe, easy to use and have virtually no toxicity issues unless put into eye • One-step O t systems t nott effective ff ti iin killi killing Acanthamoeba cysts because of rapid neutralization • Lack any conditioning agent ¾Very high wetting angle • Great for people with solution allergy AMO Complete Recall: The Facts • 46 patients developed (AK) since January 2005 • 39 of these patients wore soft contact lens • 21 of the CL wearers reported using Complete • CDC estimates at least seven times greater risk of AK for those who used Complete 11 5/26/2011 The Future AMO Complete- What happened? • Acanthamoeba ¾Shape oval to triangular when moving ¾Eukaryote- like us ¾Form cysts when stressed ¾Needs break to enter cornea ¾EPA water standards have changed • Water supplies w/ amoeboe now OK for consumption New Solutions • Dual disinfection the new standard • RevitalEyes ¾Preserved with polyquaternarium and alexidine • BioTrue ¾Preserved with polyquaternarium and PHMB ¾Addition of hyaluronan • Better lens surfaces • Better understanding of lens surface- solution interaction • Better ways to prevent & remove deposits • Better ways to condition lens surfaces • Better molecules to kill pathogens Prescribing Solutions • Prescribe, Prescribe, Prescribe • Evaluate lens material characteristics • Know potential interactions between solutions, materials • Understand that patients will change solutions unless you educate them! Conclusion • No solution works for every patient every time ! • Follow the literature as studies are published • Be critical of the intent of the authors • Use lid eversion and fluorescein staining to accurately evaluate your contact lens patients compatibility with solutions • Always consider solution-related complications or interactions when you are problem solving comfort issues 12