- Email: [email protected]
Understanding corneal permeation of lincosamide antimicrobials: in-vitro studies with synthetic stromal models
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Poster abstracts / Contact Lens & Anterior Eye 36 (2013) e16–e46
42 Understanding corneal permeation of lincosamide antimicrobials: in-vitro studies with synthetic stromal models Anisa Mahomed (PhD) ∗ , Nigel Atherton (PhD), Brian Tighe (Prof.) E-mail address: [email protected] (A. Mahomed). Purpose: Lincomycin and clindamycin are structurally related antimicrobials useful for treatment of both Gram- positive and Gram-negative anaerobes. On topical application therapeutic levels are attained in the cornea, aqueous humor, and iris-ciliary body, but despite structural similarity, behavioural differences occur. Clindamycin has higher overall concentration and shorter peak onset values in ocular tissues. This poster describes the use of in-vitro permeation through a corneal stromal model in the study of these behavioural differences. Method: High water content (ca 90%) acrylamide- based hydrogel membranes were mounted in purpose- designed permeability cells and used to determine permeation coefficients of 0.1 M clindamycin and lincomycin in the form of clinically used hydrochloride solutions. Effects of temperature and concentration were studied together with physicochemical and water structuring properties of the antibiotics. In addition the influence of the antibiotics on the water structuring of synthetic hydrogel membranes was investigated. Results: The permeability coefficient for clindamycin (60.4 ± 3.0 × 10−7 cm2 /s) was greater than that of lincomycin (34.4 ± 1.7 × 10−7 cm2 /s) at 37 ◦ C. Lincomycin showed classic fickian behaviour with respect to both concentration and temperature. However, at low temperatures and high concentrations clindamycin deviated from this behaviour. The calculated octanolwater distribution coefficient (logD) was 0.3 ± 0.5 for clindamycin and -0.7 ± 0.5 for lincomycin. Clindamycin had greater solubility (1800 ± 150 g/L) than lincomycin (875 ± 85 g/L) and self-associated at higher concentrations. Both antibiotics influenced the water structuring of artificial hydrogel membranes, but the type and extent of this was dependant on the chemical nature and freezing to non-freezing water composition of the hydrogel. Conclusions: The change in transport behaviour of clindamycin suggests the presence of complex and competitive interactions, influenced by both temperature and concentration. In-eye the increased permeation and higher tissue concentration of clindamycin is a combination of the influence of temperature, concentration and higher logD. http://dx.doi.org/10.1016/j.clae.2013.08.105 43 Comparison of the surface morphology of daily disposable silicone hydrogel contact lenses via atomic force microscopy Sibichen Thekveli (PhD) ∗ , Erich Bauman (OD MBA FAAO) E-mail address: [email protected] (S. Thekveli). Purpose: The water gradient properties of the delefilcon A (DAILIES® TOTAL1®) contact lens surface were assessed and compared to several other commercially available silicone hydrogel daily disposable contact lenses. Method: Atomic Force Microscopy (AFM) data from height, modulus and tip interaction force channels were used to elucidate the micro-structure and morphology of the surface region of
various lens types. Morphological characteristics of the test lenses, namely narafilcon A, narafilcon B, stenfilcon A, nesofilcon A, and filcon II 3, were compared with those of delefilcon A control lenses. Results: All the test lenses showed flat modulus profiles across the lens cross section, where the modulus of the lens surface region remained similar to that at the lens core. The modulus gradient, defined herein as the difference in modulus between the lens core and surface region expressed as a percentage of the core modulus, was relatively small for narafilcon A (7.46 ± 0.92%), narafilcon B (1.05 ± 1.49%), stenfilcon A (2.47 ± 0.09%), filcon II 3 (7.24 × ± 9.38%), and nesofilcon A (12.3 ± 13.63%). In contrast, delefilcon A lens showed a large modulus gradient (38.42 ± 1.69%), whose modulus decreased significantly when traversing from the core to the surface region of the lens and reached a minimum at the outermost surface of the lens. The height profile of delefilcon A was characterised by a prominent gradient in elevation (∼ 200 nm/micron of thickness) spanning the outer 6 microns of the lens surface, which is attributed to the diffusely crosslinked hydrophilic polymer network present at the surface of delefilcon A lenses. In contrast, the test lenses showed little or no elevation compared to the core of the lens. Conclusions: Delefilcon A lenses exhibited unique gradients in hydrophilic composition, surface modulus and water content across the lens cross section. The surface of delefilcon A lenses, with its characteristic, soft, brush-fibril type structures, was notably softer than the lens core and exhibited very high levels of hydration. In contrast, the test lenses did not contain a gradient morphology across the lens cross section. In addition, the soft brush type structures seen on delefilcon A lens surface were not seen on any of the test lenses. http://dx.doi.org/10.1016/j.clae.2013.08.106 OPTICS 44 Designing multifocal contact lenses using a new through-focus image quality metric and individual computer eye models Ian Cox (B.Optom., Ph.D.) ∗ , Amanda Kingston (M.S.) E-mail address: [email protected] (I. Cox). Purpose: To design a new multifocal contact lens using a novel through-focus image quality metric and individual computer eye models. Method: Individual eye models were implemented in optical design software (ZemaxTM Bellevue, WA) based on evaluation of ocular aberrations, pupil diameter, visual acuity and accommodative response of ninety subjects (180 eyes; 24 - 63 years of age). Monocular high contrast logMAR acuity was assessed at 6 m, 2 m, 1 m, 67 cm, 50 cm, 40 cm, 33 cm, 28 cm, and 25 cm. While the subject fixated on the lowest readable line of acuity, total ocular aberrations and pupil diameter were measured three times each using the Complete Ophthalmic Analysis System (COAS) at each distance. A subset of 64 advanced presbyopic eyes was used to predict the clinical logMAR acuity performance of five novel multifocal contact lens designs. To validate predictability of the design process, 5 multifocal designs were manufactured and tested clinically on a population of 24 mature presbyopes. 7 object distances were used (6 m, 2 m, 1 m, 67 cm, 50 cm, 40 cm, 25 cm) to measure monocular high contrast logMAR acuity Results: Baseline clinical through-focus logMAR was shown to correlate highly (R2 = 0.85) with predicted logMAR from individual
Poster abstracts / Contact Lens & Anterior Eye 36 (2013) e16–e46
42 Understanding corneal permeation of lincosamide antimicrobials: in-vitro studies with synthetic stromal models Anisa Mahomed (PhD) ∗ , Nigel Atherton (PhD), Brian Tighe (Prof.) E-mail address: [email protected] (A. Mahomed). Purpose: Lincomycin and clindamycin are structurally related antimicrobials useful for treatment of both Gram- positive and Gram-negative anaerobes. On topical application therapeutic levels are attained in the cornea, aqueous humor, and iris-ciliary body, but despite structural similarity, behavioural differences occur. Clindamycin has higher overall concentration and shorter peak onset values in ocular tissues. This poster describes the use of in-vitro permeation through a corneal stromal model in the study of these behavioural differences. Method: High water content (ca 90%) acrylamide- based hydrogel membranes were mounted in purpose- designed permeability cells and used to determine permeation coefficients of 0.1 M clindamycin and lincomycin in the form of clinically used hydrochloride solutions. Effects of temperature and concentration were studied together with physicochemical and water structuring properties of the antibiotics. In addition the influence of the antibiotics on the water structuring of synthetic hydrogel membranes was investigated. Results: The permeability coefficient for clindamycin (60.4 ± 3.0 × 10−7 cm2 /s) was greater than that of lincomycin (34.4 ± 1.7 × 10−7 cm2 /s) at 37 ◦ C. Lincomycin showed classic fickian behaviour with respect to both concentration and temperature. However, at low temperatures and high concentrations clindamycin deviated from this behaviour. The calculated octanolwater distribution coefficient (logD) was 0.3 ± 0.5 for clindamycin and -0.7 ± 0.5 for lincomycin. Clindamycin had greater solubility (1800 ± 150 g/L) than lincomycin (875 ± 85 g/L) and self-associated at higher concentrations. Both antibiotics influenced the water structuring of artificial hydrogel membranes, but the type and extent of this was dependant on the chemical nature and freezing to non-freezing water composition of the hydrogel. Conclusions: The change in transport behaviour of clindamycin suggests the presence of complex and competitive interactions, influenced by both temperature and concentration. In-eye the increased permeation and higher tissue concentration of clindamycin is a combination of the influence of temperature, concentration and higher logD. http://dx.doi.org/10.1016/j.clae.2013.08.105 43 Comparison of the surface morphology of daily disposable silicone hydrogel contact lenses via atomic force microscopy Sibichen Thekveli (PhD) ∗ , Erich Bauman (OD MBA FAAO) E-mail address: [email protected] (S. Thekveli). Purpose: The water gradient properties of the delefilcon A (DAILIES® TOTAL1®) contact lens surface were assessed and compared to several other commercially available silicone hydrogel daily disposable contact lenses. Method: Atomic Force Microscopy (AFM) data from height, modulus and tip interaction force channels were used to elucidate the micro-structure and morphology of the surface region of
various lens types. Morphological characteristics of the test lenses, namely narafilcon A, narafilcon B, stenfilcon A, nesofilcon A, and filcon II 3, were compared with those of delefilcon A control lenses. Results: All the test lenses showed flat modulus profiles across the lens cross section, where the modulus of the lens surface region remained similar to that at the lens core. The modulus gradient, defined herein as the difference in modulus between the lens core and surface region expressed as a percentage of the core modulus, was relatively small for narafilcon A (7.46 ± 0.92%), narafilcon B (1.05 ± 1.49%), stenfilcon A (2.47 ± 0.09%), filcon II 3 (7.24 × ± 9.38%), and nesofilcon A (12.3 ± 13.63%). In contrast, delefilcon A lens showed a large modulus gradient (38.42 ± 1.69%), whose modulus decreased significantly when traversing from the core to the surface region of the lens and reached a minimum at the outermost surface of the lens. The height profile of delefilcon A was characterised by a prominent gradient in elevation (∼ 200 nm/micron of thickness) spanning the outer 6 microns of the lens surface, which is attributed to the diffusely crosslinked hydrophilic polymer network present at the surface of delefilcon A lenses. In contrast, the test lenses showed little or no elevation compared to the core of the lens. Conclusions: Delefilcon A lenses exhibited unique gradients in hydrophilic composition, surface modulus and water content across the lens cross section. The surface of delefilcon A lenses, with its characteristic, soft, brush-fibril type structures, was notably softer than the lens core and exhibited very high levels of hydration. In contrast, the test lenses did not contain a gradient morphology across the lens cross section. In addition, the soft brush type structures seen on delefilcon A lens surface were not seen on any of the test lenses. http://dx.doi.org/10.1016/j.clae.2013.08.106 OPTICS 44 Designing multifocal contact lenses using a new through-focus image quality metric and individual computer eye models Ian Cox (B.Optom., Ph.D.) ∗ , Amanda Kingston (M.S.) E-mail address: [email protected] (I. Cox). Purpose: To design a new multifocal contact lens using a novel through-focus image quality metric and individual computer eye models. Method: Individual eye models were implemented in optical design software (ZemaxTM Bellevue, WA) based on evaluation of ocular aberrations, pupil diameter, visual acuity and accommodative response of ninety subjects (180 eyes; 24 - 63 years of age). Monocular high contrast logMAR acuity was assessed at 6 m, 2 m, 1 m, 67 cm, 50 cm, 40 cm, 33 cm, 28 cm, and 25 cm. While the subject fixated on the lowest readable line of acuity, total ocular aberrations and pupil diameter were measured three times each using the Complete Ophthalmic Analysis System (COAS) at each distance. A subset of 64 advanced presbyopic eyes was used to predict the clinical logMAR acuity performance of five novel multifocal contact lens designs. To validate predictability of the design process, 5 multifocal designs were manufactured and tested clinically on a population of 24 mature presbyopes. 7 object distances were used (6 m, 2 m, 1 m, 67 cm, 50 cm, 40 cm, 25 cm) to measure monocular high contrast logMAR acuity Results: Baseline clinical through-focus logMAR was shown to correlate highly (R2 = 0.85) with predicted logMAR from individual