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List of Speakers

Professor Dwight Cavanagh
	Department of Ophthalmology The University of Texas Southwestern Medical Centre at Dallas Title: In search of the perfect contact lens: a 40 year journey Abstract Contact lenses after all, are plastic foreign bodies that we ask the eye to tolerate cheerfully, and before breakfast too! The worst complication is and always has been lens-induced infection. Can it ever be eliminated? Of course not, for the world is covered with microbes seeking their fifteen hours of corneal fame. Is infection the fault of a contaminated lens? Or is it how the corneal surface responds to the lens that is the culprit. For many years, our laboratory has investigated this problem, particularly for the bacterial Pseudomonas Aerugionosa (PA) which is the most common (>50%) cause of lens-induced, infectious keratitis. Along the way, we discovered in both the rabbit animal model and in patients that lens oxygen values regulate binding of PA to corneal surface cells, and not lens type or wearing schedule. Hypoxia alone (no lens) does not make corneal epithelial cells bind PA more avidly but lens-induced hypoxia does! Another important finding was the unique observation that the cornea undergoes adaptation to lens wear, and that after six months, even wear of lower O2 lenses induced less PA binding. Taken together, these results suggest that the recent introduction of a whole new class of hyper oxygen transmitting lenses (silicone hydrogels, RGPs) represents a great leap forward in lens safety. There still remains however, the important question of which is better (safer): daily wear of silicone hydrogels or De Novo (no preceding daily wear) immediate fitting in extended wear? To answer this question, we will report the results of a three-year clinical trial (single center, randomized, double-masked) which examined the binding of PA to exfoliated surface corneal epithelial cells in one eye as well as corneal epithelial layer thickness in the other. Test lenses included: Ciba Night and Day (DW vs. de novo EW), Accuvue Advance (DW) and Ox Optyx (DW, de Novo EW); and, results will be compared to daily or extended wear of the Menicon Z RGP lens. Since the code on this study can not be broken until December 12, 2006 and this abstract is needed months earlier, the results will be presented at the Menicon Symposium in Singapore in March, 2007. The research team looks forward to sharing this important and exciting new information with the contact lens research community at that time.
Dr. Masaki Imayasu
	Central Research Laboratories Menicon Co., Ltd Title : Effects of multi-purpose solutions on corneal epithelial tight junctions Abstract Corneal epithelial tight junctions (zonula occuludens) play a vital role in the barrier functions protecting from microbial infections. Because hydrogel lens wearers frequently use multi-purpose solution (MPS), it is very important to confirm that a MPS does not interfere with the normal corneal epithelial integrity and barrier functions. This study compares the effects of four kinds of commercially available MPSs on the morphology and barrier function of corneal epithelial tight junctions. Human corneal epithelial cells (HCET cell) were cultured on collagen coated culture slides for 7 days, then were exposed to MPS-A (PHMB, macrogolglycerol hydroxystearate), MPS-B (PHMB, poloxamine), MPS-C (Alexidine, poloxamine) and MPS-D (Polyquad, poloxamine) for 30 to 120 min. Tight junction integrity of the corneal epithelial cells was evaluated with ZO-1 (tight junction-related protein) labeling under laser confocal microscopy. Control (without MPS treatment) and MPS-A treated epithelial cells showed normal, continuous linear pattern in ZO-1 staining along with cell-cell junctions. However, epithelial cells treated with MPS-B, MPS-C and MPS-D showed discontinuous and disrupted line structures at cell-cell borders. This may correspond to a partial breakdown of epithelial tight junctions. Disrupted structure of tight junction was also observed by 3D (X-Z) imaging using a laser confocal microscope. For quantitative evaluation of barrier functions, transepithelial electrical resistance (TER) of the epithelial cell was measured 30 and 60 min after MPS exposure, using a voltohmmeter. Treatment of epithelial monolayers with MPS-B, MPS-C and MPS-D caused a time-dependent decrease in TER, whereas there was no significant difference between MPS-A treated group and the control group (culture medium). These results suggest the possibility that frequent use of MPS with high cytotoxicity may lead to the breakdown of epithelial barrier functions and increase the risk of associated microbial infections in hydrogel lens wearers.
Professor Teruo Nishida
	Professor and Chairman Department of Biomolecular Recognition and Ophthalmology Yamaguchi University School of Medicine Japan Title: Toward the ideal contact lens care solution Abstract With the exception of daily disposable lenses and extended wear lenses, contact lenses must be cleaned and disinfected after each use. The risk of microbial keratitis is greater in a wearer of contact lenses than in a nonwearer because such lenses adversely affect the defense system of the ocular surface by preventing the clearance of debris and microorganisms, interfering with the normal protective function of the mucin layer, and serving as a vector for facilitation of infection. Multipurpose solutions (MPSs) account for more than 80% of prescribed lens care regimens worldwide. The advantages of MPSs include their simplicity of use—resulting in a reduction in the time required to train the lens wearer in their use and in good compliance of the user—as well as their compatibility with various lens materials. MPSs are designed to clean, rinse, disinfect, and preserve contact lenses, providing all of these functions in a single solution. A balance must be achieved among the various characteristics (tonicity, pH, viscosity, as well as cleaning, antimicrobial, and buffering agent composition) of MPSs, but the achievement of such a balance may reduce the effectiveness of individual components, most importantly that of the disinfectant. Optimal efficacy of antimicrobial agents tends to be achieved at concentrations that are toxic to the eye. It is thus important to balance the efficacy of disinfecting agents with their safety of use at the ocular surface and their convenience for the lens wearer. In my presentation, I will review the advantages and disadvantages of various options for the care of contact lenses and address the requirements for an ideal lens care system.
Professor Donald Tan
	Director, Singapore Eye Research Institute Deputy Director, Singapore National Eye Center Chairman, Dept of Ophthalmology, Yong Loo Lin School of Medicine, NUS Title: Unusual emerging infections affecting contact lenses Abstract Despite the advent of newer generation broad spectrum topical antibiotics, and apparent advances in new contact lens modalities and disinfection systems, a global trend in increasing and newly emerging infections of the cornea appears to be upon us, and within a background of infectious keratitis remaining the major cause of corneal transplantation in developing countries in Asia and around the world. Global outbreaks such as the recent contact lens-related fusarium outbreak, as well as a general re-emergence of acanthameba keratitis represent examples of a changing environment. At the Singapore National Eye Centre, a tertiary ophthalmic referral institution which provides eye care service delivery to much of Singapore’s developed Asian urban population as well as catering to considerable regional referrals from South East Asian communities with developing or rural populations, we are documenting a significant rise in the prevalence of infectious keratitis over the last decade, as well as emergence of hitherto unknown or rare forms of infectious keratoconjunctivitis. There has been an overall significant rise in the number of positive cultures of infectious keratitis in two of our major centres between 2000 (135 cases) and 2006 (213 cases), representing an increase by 58%. Much of these cases were due to a rise in positive cultures of Pseudomonas aeruginosa in the last 3 years (we documented a total of 176 cases over a 29 month period between April 2004 and August 2006). In addition, the contact lens-related Fusarium keratitis outbreak in 2005/2006 accounted for a major series of reported 66 cases in Singapore. More recently, we have seen an emerging epidemic in microsporidial keratoconjuncivitis, which is also beginning to appear in other countries including the Indian subcontinent. We described our first case of microsporidial keratoconjunctivitis in an immunocompetent male contact lens wearer in 2001, and described our initial series of 7 eyes in 2003. In the last 2 years, we have seen a tremendous rise in the incidence of this form of keratitis, and we now have over 50 confirmed cases in Singapore, the largest single series today. Finally, acanthameba keratitis appears to be re-emerging, with reports of increasing cases in the West, and in our centre, 58% (11/19) of our cases over the last 6 years, have occurred in the recent 2 years. Contact lens wear has been implicated as a significant risk factor for all of these conditions, to varying degrees, and it is timely to examine the true role of contact lens wear in this emerging prevalence of usual and unusual forms of infectious keratitis, with appropriate case control and cohort studies. Factors which must be examined include the impact of the changing prevalence of contact lens wear in our populations, the impact, if any, on newer contact lenses, wearing patterns, and the impact of the newer forms of contact lens disinfection systems and the impact of changing antimicrobial resistance patterns relating to the use or abuse of newer generation topical antibiotics today.
Professor Roger W. Beuerman
	Director/Scientific Director Singapore Eye Research Institute Adjunct Prof., Dept of Ophthalmology, Yong Loo Lin School of Medicine, NUS Title: Relative "killing efficacy" of contact lens solutions on F. solani isolates causing infections of differing severity Abstract Contact lens solutions undergo standardized testing to determine their killing ability for against bacteria and fungus prior to their acceptance for consumer release. The protocol ISO 14729:2001 specifies the procedures for testing the solution at full concentration against a standard strain of Fusarium solani, ATCC 36031. However, in view of the recent out-break of contact lens related fungal infections little it known about the comparative efficacy against clinical isolates. Moreover, as contact lens solutions may undergo solution stress after evaporation, it would be useful to be able to compare killing efficacy in two situations, full concentration and the half-evaporation concentration. In these studies we used contact lens solutions purchased off the shelf from the following companies: Menicon (one solution), Bausch and Lomb (two solutions), Alcon (two solutions), and Advanced Medical Optics (one solution). The ATCC strain of F. solani were compared with three clinical isolates from contact lens patients. The results from the stand-alone test at full concentration using the ATCC strain showed that at 24 hrs virtually all solutions provided the same disinfection efficacy and were able to reduce the original inoculum of about 105.5 colony forming units by about 4+ log units. However, when three clinical isolates were tested the results using the original concentration varied from just over 3 log units reduction to almost 5 log units and there was less uniformity in effect for any one of the F. solani clinical isolates. Using the half-evaporation solutions in the stand alone test there was even less agreement among solutions and organisms. The log reduction was found to be between about 2.5 to just over three for one isolate to about 1 log unit to almost 4 log units for the other two clinical isolates. In conclusion, it may be that the noted that the ATCC strain of F. solani may not adequately represent the more pathogenic F. solani strains that are affecting patients and that the stand alone test may need to be augmented by the half-evaporation test.
Dr. Chandra Verma
	Group Leader, Bioinformatics Institute of Singapore Title : Designing anti-microbial molecules Abstract Antimicrobial peptides are found as potent components of vertebrates, plants and microbes and display a range of complex antimicrobial properties. They act directly on the microbes by lysing their cells and at the same time, exert their effects indirectly by stimulating the host immune system. They are small, robust and are characterized by a rich diversity both in composition and in their effects. Knowledge of the relationship between their sequence, structure, physico-chemical properties and mode of action is being assimilated worldwide. Their small size and diverse effects make them ideal candidates for the design and development of potent novel antimicrobials. These efforts will be reviewed.
Professor Karin D. Caldwell
	Center for Surface Biotechnology Uppsala University, Sweden Title : Anti-microbial surface modification of contact lenses material Abstract Polymeric surfaces in contact with tear fluid and other mucin containing liquids will readily adsorb the large mucin molecules and thereby afford the surface new and in many cases highly desirable properties. These include increased lubricity, as well as resistance to certain protein deposition and bacterial colonization. Given that these properties are intimately linked to the surface concentration of mucin, a method for determining this concentration has been developed and will be presented. Deposition studies on commercially available contact lenses will illustrate the method. In vitro experiments involving hydrophobic model surfaces and soluble mucins of different origins will demonstrate that adsorption kinetics, film thickness, and molecular close packing vary significantly depending on the presence of contaminants such as e.g. plasma proteins. Given the increasing interest in the behavior of mucin on surfaces we strongly suggest that the product composition be given careful scrutiny before comparative deposition studies are undertaken
Professor Paul Savage
	Department of Chemistry Brigham Young University, USA Title : Designing Cationic Steroid based Antimicrobial molecules Abstract Last year’s recall of a leading contact lens solution due to increased risk of fungal infection has focused attention on the efficacy of existing products and the need for new approaches for controlling microbial growth on lenses and in storage containers. We have developed a novel class of antimicrobial agents, termed ceragenins, with broad-spectrum activities against bacteria and fungi including common ocular pathogens. Ceragenins selectively target bacterial and fungal membranes causing rapid cell death (high inocula of ocular pathogens are eradicated in less than four hours), and antimicrobial agents with this type of mechanism are not expected to engender bacterial resistance. Notably, the ceragenins are active against established biofilms. In addition to their antimicrobial activities, the water solubility and stability of ceragenins make them attractive candidates for use in contact lens disinfectant solutions.
Jackie Y.Ying
	Institute of Bioengineering and Nanotechnology Nanostructure Processing of Advanced Biomaterials Abstract Nanostructured materials are of interest for a variety of applications. Through controlled synthesis in reverse microemulsions, my laboratory has achieved polymeric nanoparticles for the glucose-sensitive delivery of insulin. These stimuli-responsive materials allow for the appropriate insulin delivery to diabetic patients only when their blood sugar levels are high, without the need for external blood sugar monitoring. We have also developed apatite-polymer nanocomposite particles for the sustained, zero-order delivery of protein therapeutics. By adsorbing valuable bone morphogenetic proteins on carbonated apatite nanocrystals that are then encapsulated within biodegradable polymeric microparticles, we are able to achieve controlled release of this growth factor for the bone healing process over an extended period of time. Functionalized nanoparticles and quantum dots have also been tailored for bioimaging, biolabeling and bioseparation applications. In addition, nanostructure processing has been employed in artificial implant and tissue engineering applications. For example, nanocomposite processing has been applied to obtain orthopedic implants and bone scaffolds with superior mechanical strength and bioactivity. By combining microfabrication and nanotechnology, we have also created various microstructures in kidney-specific dimensions and shapes. These structures can be used as bioartificial renal assist microdevices, and may serve as three-dimensional templates for tissue engineering.