43 longitudinal study of ocular manifestations on a cohort of non-related fabry's disease...
TRANSCRIPT
Abstracts of the 2011 BCLA Annual Clinical Conference / Contact Lens & Anterior Eye 34, Supplement 1 (2011) S1–S43 S27
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Longitudinal study of ocular manifestations on a cohort of non-relatedFabry’s disease patients: new findings and early results
Langis Michaud
Université de Montréal, Montréal, Canada
E-mail address: [email protected]
Purpose: This unique studywas started inMarch 2010 as part of the CanadianFabry’s Disease Registry and aims to determine the evolution of ocular man-ifestations over five years related to the sex, the type of genetic mutations,and the effect of enzyme substitution treatment if present. It also aims to in-crease awareness among eyecare practitioners about ocular manifestationsrelated to Fabry’s disease.
Method:Subjects (25) were referred by the only genetician who treatsFabry’s disease in Quebec province. Clinical evaluation includes refraction,optical aberration measurements, slit lamp, topography, anterior/posteriorsegment OCT, anterior/posterior segment photography, threshold visualfields and corneal hysteresis/IOP.
Results: There is a huge inter- and intra-subject variation of the clinicalsigns observed. Overall, male Fabry subjects affected for a longer time showmore severe ocular manifestations. Corneal aberrations, visual fields, hys-teresis and IOP are not different from normal subjects. In more advancedcases, a new clinical sign seems to emerge: external superior upper lid ves-sels tortuosity is present compared with normal subjects. A grading of thisnew clinical manifestation is proposed.
Conclusions: Fabry’s, if left undetected and untreated, is a life-threateningdisease. This unique study project already helped to identify seven new sub-jects affected by the disease and to impact on their quality of life. Clinicaldata gathered after almost one year, on a unique large sample of non-relatedpatients, helped to determine the occurrence, prevalence and severity of oc-ular manifestations related to several factors. More important, a new clinicalfinding, never reported before, was found.
SOLUTIONS
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Relative lipid deposition by daily wear adverse-event subjects for twomultipurpose solutions
Charles H Powell*, Eugenia Kao, James Cook, Adriana Park, Linda Tsai
Abbott Medical Optics Inc., Santa Ana, CA, USA
*E-mail address: [email protected]
Purpose: To assess lipid levels of soft contact lenses from a clinical study com-paring twomarketed multipurpose disinfection solutions (MPDS)with 5 lenstypes and then determine if patients exhibiting an adverse event (AE, anyevent causing termination) display atypical lipid deposit levels.
Method: In a three-month, multi-site, double-masked clinical comparisonof an Alexidine/Polyquaternium-1 (ALX/PQ1, Test) vs. an Aldox/PQ1 (Control)MPDS, right lenses from 247 subjects, taken at the end of a prescribed weartime (≥2 wks) or at time of AE, were quantified for total lipid by FTIR analy-sis (C-H stretch at 2916 cm-1) of the lens extract (toluene:IPA; 4:1) depositedonto an IR-transparent membrane.
Results: Subjects assigned Test were double those assigned ControlMPDS; and AE incidence was 2.8% (5 subjects) for Test vs. 12.9% (11 sub-jects) for the Control arm. Average lipid level and type varied per lens type.No significant difference in lipid level for the overall patient population wasfound for Test vs. Control (p≥0.18 per lens type); however, AE subjects usingthe Control were significantly above the 60 percentile (p=0.046, binomial ex-act test) in lipid deposits as assessed per lens type. Average lipid ranking forAE subjects using Control MPDS was 78 (±17) percentile.
Conclusions: Adverse-event subjects using the Control (Aldox/PQ1) MPDSwere assessed to be significantly above the 60 percentile for lipid depositlevel. This trend was not observed for the Test (Alexidine/PQ1) MPDS, al-though the AE data set for the Test was smaller (five lenses).
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Effect of contact lens solutions on the structure and function of tearproteinsextracted fromworn contact lenses
Curtis B Dobson*, Philip B Morgan, Carole Maldonado-Codina, Karl A P Payne
University of Manchester, Manchester, UK
*E-mail address: [email protected]
Purpose: It has been proposed that denaturation of proteins accumulatingon and within soft contact lenses during wear may reduce beneficial func-tion including antimicrobial activity. We therefore investigated the extent ofdenaturation and direct antimicrobial activity of proteins extracted from exvivo lenses and the effect of treatment of lenses with different contact lenssolutions on these properties.
Method: Worn and unworn hydrogel soft contact lenses were treatedovernight with either a hydrogen peroxide-based solution (Oxysept 1 step,AMO) or an investigational formulation of a novel multipurpose solutioncontaining protein stabilizing agents (Biotrue, Bausch+Lomb) (iMPS), priorto tear protein extraction. The structural integrity of lysozyme from wornlenses was assessed by measuring rapid lytic activity againstMicrococcus lu-teus. In addition, the functional integrity of the extracted lens proteins wastested directly, by challenging with suspensions of Pseudomonas aeruginosa(ATCC 9027) and Staphylococcus aureus (ATCC 6538).
Results: The structural integrity of recovered lysozyme appeared signifi-cantly reduced after use of the peroxide- based solution relative to that afterusage of the iMPS. Direct incubation with extracts resulted in a 2 to 3 logdecrease in cell viability (compared with extracts from unworn lenses). Thisactivity was largely maintained after usage of the iMPS, but was strongly in-hibited after usage of the peroxide-based lens solution.
Conclusions: We found that the peroxide-based solution disrupted tearprotein structure and function relative to that after usage of the iMPS, sug-gesting that usage of different contact lens solutions may differentially im-pact denaturation state and potential beneficial function of absorbed tearproteins.
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Effects of multipurpose disinfecting solutions on corneal cell physiologyexamined by confocal microscopy
Nerida Cole1,*, Linda Garthwaite1, Mark DPWillcox2
1Brien Holden Vision Institute, Sydney, Australia; 2University of New SouthWales, Sydney, Australia
*E-mail address: [email protected]
Purpose: The use of certain multipurpose disinfecting solutions (MPDS) withcertain silicone hydrogel contact lenses is associatedwith corneal infiltrativeevents. This study examines the effects of time of exposure and concentra-tions of MPDS on human corneal limbal epithelial (HCLE) cells’ metabolicactivity, membrane integrity and apoptosis.
Method: HCLE were exposed to dilutions (0–20%) of two MPDS(Polyquat/Aldox) for 2, 6 and 18 hours. Cells were enumerated usingCyquant, cell metabolismwas quantified usingMTT assay and cell membraneintegrity and necrotic/ apoptotic cells examined by fluorescent scanning con-focal scanning laser microscopy.
Results: Exposure of HCLE for two hours to either MPDS resulted in de-creases in adherent cell numbers of up to 40% and increases in non-viablecells of up to 50%. By 18 hours there were reductions in cell numbers ofup to 2.5-fold with significant differences between each MPDS. Confocal mi-croscopy revealed alterations in cell morphology which differed between so-lutions and may be associated with differing mechanisms of cell damage.
Conclusions: Exposure of cells to MPDS at concentrations above 5% re-sulted in time dependent alterations in cell morphology andmetabolic activ-ity which are solution dependent. Further investigation may lead to a betterunderstanding of interactions between corneal cells and MPDS.