The Experts below are selected from a list of 300 Experts worldwide ranked by ideXlab platform
Keith M. Meek - One of the best experts on this subject based on the ideXlab platform.
-
Elastic microfibril distribution in the Cornea: Differences between normal and keratoconic stroma ☆
Experimental eye research, 2017Co-Authors: Tomas White, Robert D Young, Koji Kitazawa, Tsutomu Inatomi, Shigeru Kinoshita, Philip N. Lewis, Keith M. MeekAbstract:The optical and biomechanical properties of the Cornea are largely governed by the collagen-rich stroma, a layer that represents approximately 90% of the total thickness. Within the stroma, the specific arrangement of superimposed lamellae provides the tissue with tensile strength, whilst the spatial arrangement of individual collagen fibrils within the lamellae confers transparency. In keratoconus, this precise stromal arrangement is lost, resulting in ectasia and visual impairment. In the normal Cornea, we previously characterised the three-dimensional arrangement of an elastic fiber network spanning the posterior stroma from Limbus-to-Limbus. In the peripheral Cornea/Limbus there are elastin-containing sheets or broad fibers, most of which become microfibril bundles (MBs) with little or no elastin component when reaching the central Cornea. The purpose of the current study was to compare this network with the elastic fiber distribution in post-surgical keratoconic Corneal buttons, using serial block face scanning electron microscopy and transmission electron microscopy. We have demonstrated that the MB distribution is very different in keratoconus. MBs are absent from a region of stroma anterior to Descemet's membrane, an area that is densely populated in normal Cornea, whilst being concentrated below the epithelium, an area in which they are absent in normal Cornea. We contend that these latter microfibrils are produced as a biomechanical response to provide additional strength to the anterior stroma in order to prevent tissue rupture at the apex of the cone. A lack of MBs anterior to Descemet's membrane in keratoconus would alter the biomechanical properties of the tissue, potentially contributing to the pathogenesis of the disease.
-
Immunochemical localization of keratan sulfate proteoglycans in Cornea, sclera, and Limbus using a keratanase-generated neoepitope monoclonal antibody.
Investigative ophthalmology & visual science, 2008Co-Authors: Saeed Akhtar, Briedgeen Kerr, Anthony Joseph Hayes, Clare Elizabeth Hughes, Keith M. Meek, Bruce CatersonAbstract:PURPOSE. To evaluate the use of neoepitope monoclonal antibody BKS-1, which recognizes keratanase-generated keratan sulfate (KS) stubs on keratan sulfate proteoglycans in human Cornea, Limbus, and sclera. METHODS. BKS-1 specifically recognizes a keratanase-generated neoepitope [N-acetyl-glucosamine-6-sulfate (GlcNAc-6-S)] at the nonreducing terminal of Corneal and skeletal KS glycosaminoglycan chains. It was produced by using keratanase-digested KS peptides from bovine cartilage aggrecan as the immunizing antigen. BKS-1 was used in conjunction with 5D4 to analyze the KS distribution in human Cornea, Limbus, and sclera using Western blotting, immunohistochemistry, and electron microscopy. RESULTS. 5D4 Western blot analysis displayed a diffuse staining pattern, and it was difficult to distinguish differences among Cornea, sclera, and Limbus. However, BKS-1 showed differences in KS levels, with higher levels in the Cornea and lower levels in the Limbus and sclera. Ultrastructural studies showed that the monoclonal antibody (mAb) BKS-1 neoepitope was not observed in the epithelium or basement membrane; however, 5D4 was present in these layers. Large quantities of both antibodies were present in Bowman's layer, stroma, and Descemet's membrane, but the quantity of 5D4 was significantly higher (P < 0.001) than the quantity of BKS-1 in all these layers of the Cornea. CONCLUSIONS. mAb 5D4 recognizes oversulfated structures within KS chains, whereas BKS-1 recognizes a single neoepitope on KS after keratanase digestion of monosulfated KS disaccharides. With the use of BKS-1, the authors identified a more clearly defined pattern for KS distribution in the Cornea than was seen with 5D4. The presence of a large quantity of BKS-1 immunostaining in the Cornea suggests that KS-substituted proteoglycans are more prevalent in the Cornea than in the Limbus or sclera.
-
Mapping collagen organization in the human Cornea : Left and right eyes are structurally distinct
Investigative ophthalmology & visual science, 2006Co-Authors: Craig Boote, Sally Hayes, Mohammad Abahussin, Keith M. MeekAbstract:PURPOSE. Aspects of the biomechanics and surface topography of fellow human Corneas are known to exhibit midline symmetry, but the structural basis of these observations is poorly understood. The mechanical performance of the Cornea is strongly influenced by the organization of stromal collagen fibrils. The present study was designed to examine and compare the organization of collagen fibrils in the Corneal stroma of left and right eyes. METHODS. Wide-angle x-ray scattering was used to map in detail the orientation and distribution of fibrillar collagen across the Cornea, Limbus, and adjacent sclera of three normal human eyes, including a fellow pair, and the central 9-mm Corneal region of a further four eyes. RESULTS. Fibrillar collagen in the human Cornea and Limbus is arranged anisotropically, and in a highly specific manner. Left and right Corneas are structurally distinct. In general, the mass distribution of preferentially aligned fibrils in the Cornea appears to exhibit a degree of midline symmetry between left and right eyes. CONCLUSIONS. Structural information, such as that presented herein, will enable a better understanding of Corneal biomechanics and shape. Midline symmetry in the distribution of aligned, mechanically reinforcing collagen fibrils between left and right eyes may relate to the biomechanical and topographical enantiomorphism reported in the literature.
-
x ray scattering used to map the preferred collagen orientation in the human Cornea and Limbus
Structure, 2004Co-Authors: Hossein Aghamohammadzadeh, Richard Hugh Newton, Keith M. MeekAbstract:Many properties of connective tissues are governed by the organization of the constituent collagen. For example, the organization of collagen in the Cornea and the Limbus, where the Cornea and sclera meet, is an important determinant of Corneal curvature and hence of the eye's focusing power. We have used synchrotron X-ray scattering to map the orientation of the collagen fibrils throughout the human Cornea, Limbus, and adjacent sclera. We demonstrate a preferred orientation of collagen in the vertical and horizontal directions that is maintained to within about 1 mm from the Limbus, where a circular or tangential disposition of fibrils occurs. The data are also used to map the relative distribution of both the total and the preferentially aligned collagen in different parts of the tissue, revealing considerable anisotropy. The detailed structural information provided is an important step toward understanding the shape and the mechanical properties of the tissue.
-
CircumCorneal annulus of collagen fibrils in the human Limbus.
Investigative ophthalmology & visual science, 1998Co-Authors: R H Newton, Keith M. MeekAbstract:PURPOSE. To quantify the orientation of the collagen fibrils in the human Limbus and to compare it with the orientation in the Cornea and the sclera. METHODS. Fibril orientation was measured from 100 synchrotron x-ray diffraction patterns collected at intervals along lines across the Cornea, Limbus, and sclera. RESULTS. A distinct circumCorneal annulus of collagen fibrils was revealed in the Limbus. For the individual Cornea investigated, the annulus was not uniform around the Corneal circumference; its width, fibril angular spread, and fibril density all varied with position. The average width of the annulus was narrower in the superior sector (1.5 mm) than in the inferior sector (2.0 mm). The results from the edge of the Cornea suggested that the preferentially aligned Cornea fibrils bend sharply at the Limbus to run circumferentially or that, together with this bending or alone, extra fibrils arising in the sclera run across this zone. In the Cornea the biaxial preferred directions became more pronounced from the center of the Cornea toward the Limbus along the superior-inferior axis. CONCLUSIONS. The excess of circumferential fibrils in the Limbus, predicted from the sharp change of curvature in the surface of the eye at the Limbus, appeared to take the form of a well-defined annulus. From a consideration of the mechanics of the system it seemed probable that the purpose of this annulus was to help maintain the correct curvature of the Cornea. Before further research, it was hypothesized that some refractive problems associated with an incorrect curvature of the Cornea may be related in part to abnormalities of this circumcornecal annulus.
Christophe Baudouin - One of the best experts on this subject based on the ideXlab platform.
-
Reduced in vivo Ocular Surface Toxicity with Polyquad-Preserved Travoprost versus Benzalkonium-Preserved Travoprost or Latanoprost Ophthalmic Solutions
Ophthalmic Research, 2012Co-Authors: Hong Liang, Françoise Brignole-baudouin, Luisa Riancho, Christophe BaudouinAbstract:The study used a validated acute in vivo model to compare a new formulation of travoprost 0.004% ophthalmic solution(travoprost PQ), preserved with polyquaternium-1 (PQ), with commercially available formulations of benzalkonium-chloride(BAK)-preserved travoprost 0.004% ophthalmic solution(travoprost BAK) and BAK-preserved latanoprost 0.005%ophthalmic solution (latanoprost BAK). Adult male New Zealand albino rabbits (n = 36) were randomly divided into 6 groups. Phosphate-buffered saline (PBS), 0.001% PQ, 0.015% BAK, travoprost PQ, travoprost BAK or latanoprost BAK were applied onto rabbit eyes as 1 drop, for 15 times at 5-min intervals.The ocular surface reactions were investigated at hour 4 and day 1 using slitlamp examination; in vivo confocal microscopy (IVCM) for Cornea, Limbus and conjunctiva/conjunctiva-associated lymphoid tissue, conjunctival impression cytology and standard immunohistology in cryosections for detecting CD45+ infiltrating cells and MUC-5AC-labeled cells. PBS, PQ and travoprost PQ did not induce obvious irritation by clinical observation, changes in microstructures of the whole ocular surface as measured by IVCM analysis,inflammatory infiltration or cell damage as measured by impression cytology, altered levels of goblet cell counts or numerous CD45+ cells in the Cornea. In contrast, all BAK-containing products induced diffuse conjunctival hyperemia and chemosis, abnormal changes in the ocular surface microstructure,significant total ocular surface toxicity scores,damaged epithelial cells, inflammatory cell infiltration and decreased goblet cell density. Travoprost PQ did not elicitocular surface toxicity when administered to rabbit eyes.These results suggest a greater safety advantage for the ocular surface of patients receiving chronic glaucoma treatment with PQ-preserved drugs.
-
Polyquad-preserved travoprost/timolol, benzalkonium chloride (BAK)-preserved travoprost/timolol, and latanoprost/timolol in fixed combinations: a rabbit ocular surface study
Advances in Therapy, 2011Co-Authors: Hong Liang, Françoise Brignole-baudouin, Luisa Riancho, Aude Pauly, Christophe BaudouinAbstract:Introduction The aim of this study was to use a validated acute rabbit model to test the toxicity of a novel formulation of fixed-combination travoprost 0.004%/timolol 0.5% ophthalmic solution, which contains the antimicrobial preservative polyquaternium-1 (PQ), compared with the commercial formulation of fixed combinations travoprost 0.004%/timolol 0.5% ophthalmic solution and latanoprost 0.005%/timolol 0.5% ophthalmic solution, which both contain the preservative benzalkonium chloride (BAK). Methods Adult male New Zealand albino rabbits ( n =24) were randomly divided into four groups. Phosphatebuffered saline (PBS), travoprost/timolol PQ, travoprost/timolol BAK, or latanoprost/timolol BAK were instilled onto rabbit eyes one drop, 15 times at 5 minute intervals. The ocular surface reactions were investigated at hour 4 and day 1 using slit lamp examination; in-vivo confocal microscopy (IVCM) for Cornea, Limbus, and conjunctiva-associated lymphoid tissue (CALT); conjunctival impression cytology; and standard immunohistology in cryosections for detecting CD45+ infiltrating cells and MUC-5AC-labeled cells. Results Travoprost/timolol PQ was better tolerated than travoprost/timolol BAK or latanoprost/timolol BAK. This improved tolerance was evident via clinical observation under slit lamp, IVCM in different layers of the Cornea and conjunctiva, conjunctival impression cytology of superficial epithelium aspects, and immunohistochemistry for inflammatory infiltration of CD45+ cells in the Cornea and goblet cell distribution. Travoprost/timolol PQ was similar to PBS in regards to in-vivo findings, the Draize test for ocular irritation, and epithelial and limbal aspects as evaluated with IVCM. Treatment with either travoprost/timolol PQ or PBS produced no obvious inflammatory infiltration inside and outside the CALT follicles, yielded similar IVCM toxicity scores and CD45+ cell counts, and eyes treated with either solution had normal goblet cells. Conclusion The fixed combination of travoprost/timolol with 0.001% PQ had decreased ocular surface toxicity relative to the BAK-containing solutions. The potential benefit to the human ocular surface with oncedaily dosing needs to be evaluated clinically.
-
Comparison of the ocular tolerability of a latanoprost cationic emulsion versus conventional formulations of prostaglandins: an in vivo toxicity assay.
Molecular vision, 2009Co-Authors: Hong Liang, Christophe Baudouin, Marie-odile Faure, Gregory Lambert, Françoise Brignole-baudouinAbstract:Purpose: Using an established rabbit toxicological model, this in vivo study compared the ocular cytotoxicity of four topical intraocular pressure (IOP)-lowering agents: the commercial benzalkonium chloride (BAC)-containing solutions of 0.005% latanoprost, 0.004% travoprost, 0.03% bimatoprost (containing 0.02%, 0.015%, and 0.005% BAC, respectively), and 0.005% latanoprost in a new cationic emulsion (LCEm) formulation. Methods: Thirty adult male New Zealand albino rabbits were used in this study. They were randomly divided into five groups: 50 µl of sterile phosphate-buffered saline (PBS) along with each formulation was applied onto rabbit eyes 15 times at 5 min intervals. The ocular surface changes were investigated using slit-lamp examination, Corneal in vivo confocal microscopy (IVCM) for Cornea, Limbus, conjunctiva/conjunctiva-associated lymphoid tissue (CALT) investigations, and conjunctival imprints for cytology and flow cytometry (FCM) analyses. Results: Antiglaucoma eye drops induced an ocular surface cytotoxicity primarily related to the concentration of their common BAC preservative (0.02%BAC+latanoprost> 0.015%BAC+travoprost> 0.005%BAC+bimatoprost). LCEm did not induce any obvious signs of toxicity on the rabbit ocular surface with results similar to those of PBS; moreover, the conjunctiva/ CALT and Cornea had almost normal aspects. Conclusions: These in vivo and ex vivo toxicological procedures performed in an acute stress model confirmed the ocular surface cytotoxicity of BAC-containing antiglaucomatous eye drop solutions. The new formulation, LCEm, was well tolerated without inducing ocular surface damage or CALT activation. The cationic emulsion of latanoprost will most likely have fewer long-term adverse effects on the ocular surface than formulations containing toxic preservative BAC and may improve long-term tolerance over BAC-containing antiglaucomatous topical treatments.
Hong Liang - One of the best experts on this subject based on the ideXlab platform.
-
Reduced in vivo Ocular Surface Toxicity with Polyquad-Preserved Travoprost versus Benzalkonium-Preserved Travoprost or Latanoprost Ophthalmic Solutions
Ophthalmic Research, 2012Co-Authors: Hong Liang, Françoise Brignole-baudouin, Luisa Riancho, Christophe BaudouinAbstract:The study used a validated acute in vivo model to compare a new formulation of travoprost 0.004% ophthalmic solution(travoprost PQ), preserved with polyquaternium-1 (PQ), with commercially available formulations of benzalkonium-chloride(BAK)-preserved travoprost 0.004% ophthalmic solution(travoprost BAK) and BAK-preserved latanoprost 0.005%ophthalmic solution (latanoprost BAK). Adult male New Zealand albino rabbits (n = 36) were randomly divided into 6 groups. Phosphate-buffered saline (PBS), 0.001% PQ, 0.015% BAK, travoprost PQ, travoprost BAK or latanoprost BAK were applied onto rabbit eyes as 1 drop, for 15 times at 5-min intervals.The ocular surface reactions were investigated at hour 4 and day 1 using slitlamp examination; in vivo confocal microscopy (IVCM) for Cornea, Limbus and conjunctiva/conjunctiva-associated lymphoid tissue, conjunctival impression cytology and standard immunohistology in cryosections for detecting CD45+ infiltrating cells and MUC-5AC-labeled cells. PBS, PQ and travoprost PQ did not induce obvious irritation by clinical observation, changes in microstructures of the whole ocular surface as measured by IVCM analysis,inflammatory infiltration or cell damage as measured by impression cytology, altered levels of goblet cell counts or numerous CD45+ cells in the Cornea. In contrast, all BAK-containing products induced diffuse conjunctival hyperemia and chemosis, abnormal changes in the ocular surface microstructure,significant total ocular surface toxicity scores,damaged epithelial cells, inflammatory cell infiltration and decreased goblet cell density. Travoprost PQ did not elicitocular surface toxicity when administered to rabbit eyes.These results suggest a greater safety advantage for the ocular surface of patients receiving chronic glaucoma treatment with PQ-preserved drugs.
-
Polyquad-preserved travoprost/timolol, benzalkonium chloride (BAK)-preserved travoprost/timolol, and latanoprost/timolol in fixed combinations: a rabbit ocular surface study
Advances in Therapy, 2011Co-Authors: Hong Liang, Françoise Brignole-baudouin, Luisa Riancho, Aude Pauly, Christophe BaudouinAbstract:Introduction The aim of this study was to use a validated acute rabbit model to test the toxicity of a novel formulation of fixed-combination travoprost 0.004%/timolol 0.5% ophthalmic solution, which contains the antimicrobial preservative polyquaternium-1 (PQ), compared with the commercial formulation of fixed combinations travoprost 0.004%/timolol 0.5% ophthalmic solution and latanoprost 0.005%/timolol 0.5% ophthalmic solution, which both contain the preservative benzalkonium chloride (BAK). Methods Adult male New Zealand albino rabbits ( n =24) were randomly divided into four groups. Phosphatebuffered saline (PBS), travoprost/timolol PQ, travoprost/timolol BAK, or latanoprost/timolol BAK were instilled onto rabbit eyes one drop, 15 times at 5 minute intervals. The ocular surface reactions were investigated at hour 4 and day 1 using slit lamp examination; in-vivo confocal microscopy (IVCM) for Cornea, Limbus, and conjunctiva-associated lymphoid tissue (CALT); conjunctival impression cytology; and standard immunohistology in cryosections for detecting CD45+ infiltrating cells and MUC-5AC-labeled cells. Results Travoprost/timolol PQ was better tolerated than travoprost/timolol BAK or latanoprost/timolol BAK. This improved tolerance was evident via clinical observation under slit lamp, IVCM in different layers of the Cornea and conjunctiva, conjunctival impression cytology of superficial epithelium aspects, and immunohistochemistry for inflammatory infiltration of CD45+ cells in the Cornea and goblet cell distribution. Travoprost/timolol PQ was similar to PBS in regards to in-vivo findings, the Draize test for ocular irritation, and epithelial and limbal aspects as evaluated with IVCM. Treatment with either travoprost/timolol PQ or PBS produced no obvious inflammatory infiltration inside and outside the CALT follicles, yielded similar IVCM toxicity scores and CD45+ cell counts, and eyes treated with either solution had normal goblet cells. Conclusion The fixed combination of travoprost/timolol with 0.001% PQ had decreased ocular surface toxicity relative to the BAK-containing solutions. The potential benefit to the human ocular surface with oncedaily dosing needs to be evaluated clinically.
-
Comparison of the ocular tolerability of a latanoprost cationic emulsion versus conventional formulations of prostaglandins: an in vivo toxicity assay.
Molecular vision, 2009Co-Authors: Hong Liang, Christophe Baudouin, Marie-odile Faure, Gregory Lambert, Françoise Brignole-baudouinAbstract:Purpose: Using an established rabbit toxicological model, this in vivo study compared the ocular cytotoxicity of four topical intraocular pressure (IOP)-lowering agents: the commercial benzalkonium chloride (BAC)-containing solutions of 0.005% latanoprost, 0.004% travoprost, 0.03% bimatoprost (containing 0.02%, 0.015%, and 0.005% BAC, respectively), and 0.005% latanoprost in a new cationic emulsion (LCEm) formulation. Methods: Thirty adult male New Zealand albino rabbits were used in this study. They were randomly divided into five groups: 50 µl of sterile phosphate-buffered saline (PBS) along with each formulation was applied onto rabbit eyes 15 times at 5 min intervals. The ocular surface changes were investigated using slit-lamp examination, Corneal in vivo confocal microscopy (IVCM) for Cornea, Limbus, conjunctiva/conjunctiva-associated lymphoid tissue (CALT) investigations, and conjunctival imprints for cytology and flow cytometry (FCM) analyses. Results: Antiglaucoma eye drops induced an ocular surface cytotoxicity primarily related to the concentration of their common BAC preservative (0.02%BAC+latanoprost> 0.015%BAC+travoprost> 0.005%BAC+bimatoprost). LCEm did not induce any obvious signs of toxicity on the rabbit ocular surface with results similar to those of PBS; moreover, the conjunctiva/ CALT and Cornea had almost normal aspects. Conclusions: These in vivo and ex vivo toxicological procedures performed in an acute stress model confirmed the ocular surface cytotoxicity of BAC-containing antiglaucomatous eye drop solutions. The new formulation, LCEm, was well tolerated without inducing ocular surface damage or CALT activation. The cationic emulsion of latanoprost will most likely have fewer long-term adverse effects on the ocular surface than formulations containing toxic preservative BAC and may improve long-term tolerance over BAC-containing antiglaucomatous topical treatments.
Françoise Brignole-baudouin - One of the best experts on this subject based on the ideXlab platform.
-
Reduced in vivo Ocular Surface Toxicity with Polyquad-Preserved Travoprost versus Benzalkonium-Preserved Travoprost or Latanoprost Ophthalmic Solutions
Ophthalmic Research, 2012Co-Authors: Hong Liang, Françoise Brignole-baudouin, Luisa Riancho, Christophe BaudouinAbstract:The study used a validated acute in vivo model to compare a new formulation of travoprost 0.004% ophthalmic solution(travoprost PQ), preserved with polyquaternium-1 (PQ), with commercially available formulations of benzalkonium-chloride(BAK)-preserved travoprost 0.004% ophthalmic solution(travoprost BAK) and BAK-preserved latanoprost 0.005%ophthalmic solution (latanoprost BAK). Adult male New Zealand albino rabbits (n = 36) were randomly divided into 6 groups. Phosphate-buffered saline (PBS), 0.001% PQ, 0.015% BAK, travoprost PQ, travoprost BAK or latanoprost BAK were applied onto rabbit eyes as 1 drop, for 15 times at 5-min intervals.The ocular surface reactions were investigated at hour 4 and day 1 using slitlamp examination; in vivo confocal microscopy (IVCM) for Cornea, Limbus and conjunctiva/conjunctiva-associated lymphoid tissue, conjunctival impression cytology and standard immunohistology in cryosections for detecting CD45+ infiltrating cells and MUC-5AC-labeled cells. PBS, PQ and travoprost PQ did not induce obvious irritation by clinical observation, changes in microstructures of the whole ocular surface as measured by IVCM analysis,inflammatory infiltration or cell damage as measured by impression cytology, altered levels of goblet cell counts or numerous CD45+ cells in the Cornea. In contrast, all BAK-containing products induced diffuse conjunctival hyperemia and chemosis, abnormal changes in the ocular surface microstructure,significant total ocular surface toxicity scores,damaged epithelial cells, inflammatory cell infiltration and decreased goblet cell density. Travoprost PQ did not elicitocular surface toxicity when administered to rabbit eyes.These results suggest a greater safety advantage for the ocular surface of patients receiving chronic glaucoma treatment with PQ-preserved drugs.
-
Polyquad-preserved travoprost/timolol, benzalkonium chloride (BAK)-preserved travoprost/timolol, and latanoprost/timolol in fixed combinations: a rabbit ocular surface study
Advances in Therapy, 2011Co-Authors: Hong Liang, Françoise Brignole-baudouin, Luisa Riancho, Aude Pauly, Christophe BaudouinAbstract:Introduction The aim of this study was to use a validated acute rabbit model to test the toxicity of a novel formulation of fixed-combination travoprost 0.004%/timolol 0.5% ophthalmic solution, which contains the antimicrobial preservative polyquaternium-1 (PQ), compared with the commercial formulation of fixed combinations travoprost 0.004%/timolol 0.5% ophthalmic solution and latanoprost 0.005%/timolol 0.5% ophthalmic solution, which both contain the preservative benzalkonium chloride (BAK). Methods Adult male New Zealand albino rabbits ( n =24) were randomly divided into four groups. Phosphatebuffered saline (PBS), travoprost/timolol PQ, travoprost/timolol BAK, or latanoprost/timolol BAK were instilled onto rabbit eyes one drop, 15 times at 5 minute intervals. The ocular surface reactions were investigated at hour 4 and day 1 using slit lamp examination; in-vivo confocal microscopy (IVCM) for Cornea, Limbus, and conjunctiva-associated lymphoid tissue (CALT); conjunctival impression cytology; and standard immunohistology in cryosections for detecting CD45+ infiltrating cells and MUC-5AC-labeled cells. Results Travoprost/timolol PQ was better tolerated than travoprost/timolol BAK or latanoprost/timolol BAK. This improved tolerance was evident via clinical observation under slit lamp, IVCM in different layers of the Cornea and conjunctiva, conjunctival impression cytology of superficial epithelium aspects, and immunohistochemistry for inflammatory infiltration of CD45+ cells in the Cornea and goblet cell distribution. Travoprost/timolol PQ was similar to PBS in regards to in-vivo findings, the Draize test for ocular irritation, and epithelial and limbal aspects as evaluated with IVCM. Treatment with either travoprost/timolol PQ or PBS produced no obvious inflammatory infiltration inside and outside the CALT follicles, yielded similar IVCM toxicity scores and CD45+ cell counts, and eyes treated with either solution had normal goblet cells. Conclusion The fixed combination of travoprost/timolol with 0.001% PQ had decreased ocular surface toxicity relative to the BAK-containing solutions. The potential benefit to the human ocular surface with oncedaily dosing needs to be evaluated clinically.
-
Comparison of the ocular tolerability of a latanoprost cationic emulsion versus conventional formulations of prostaglandins: an in vivo toxicity assay.
Molecular vision, 2009Co-Authors: Hong Liang, Christophe Baudouin, Marie-odile Faure, Gregory Lambert, Françoise Brignole-baudouinAbstract:Purpose: Using an established rabbit toxicological model, this in vivo study compared the ocular cytotoxicity of four topical intraocular pressure (IOP)-lowering agents: the commercial benzalkonium chloride (BAC)-containing solutions of 0.005% latanoprost, 0.004% travoprost, 0.03% bimatoprost (containing 0.02%, 0.015%, and 0.005% BAC, respectively), and 0.005% latanoprost in a new cationic emulsion (LCEm) formulation. Methods: Thirty adult male New Zealand albino rabbits were used in this study. They were randomly divided into five groups: 50 µl of sterile phosphate-buffered saline (PBS) along with each formulation was applied onto rabbit eyes 15 times at 5 min intervals. The ocular surface changes were investigated using slit-lamp examination, Corneal in vivo confocal microscopy (IVCM) for Cornea, Limbus, conjunctiva/conjunctiva-associated lymphoid tissue (CALT) investigations, and conjunctival imprints for cytology and flow cytometry (FCM) analyses. Results: Antiglaucoma eye drops induced an ocular surface cytotoxicity primarily related to the concentration of their common BAC preservative (0.02%BAC+latanoprost> 0.015%BAC+travoprost> 0.005%BAC+bimatoprost). LCEm did not induce any obvious signs of toxicity on the rabbit ocular surface with results similar to those of PBS; moreover, the conjunctiva/ CALT and Cornea had almost normal aspects. Conclusions: These in vivo and ex vivo toxicological procedures performed in an acute stress model confirmed the ocular surface cytotoxicity of BAC-containing antiglaucomatous eye drop solutions. The new formulation, LCEm, was well tolerated without inducing ocular surface damage or CALT activation. The cationic emulsion of latanoprost will most likely have fewer long-term adverse effects on the ocular surface than formulations containing toxic preservative BAC and may improve long-term tolerance over BAC-containing antiglaucomatous topical treatments.
Manuel Doblaré - One of the best experts on this subject based on the ideXlab platform.
-
A numerical model of the eye for simulation of Corneal surgery and Corneal biomechanical properties
Acta Ophthalmologica, 2010Co-Authors: Ma Del Buey, Elena Lanchares, Ja Cristobal Bescos, Begoña Calvo, Fj Ascaso, C Palomino, L Lavilla, Manuel DoblaréAbstract:Purpose To obtain a numerical model of the ocular globe in order to simulate different Corneal surgery techniques and to measure changes in geometry and mechanical properties of the Cornea. Methods A biomechanical Finite Element model was created with the geometry of the anterior half of the ocular globe. Each part (Cornea, Limbus and sclera) has different material properties, and behaviours as hyperelastic anisotropic material. The reference configuration is achieved with initial stresses and then applied the mean physiological intraocular pressure (15 mmHg) during the whole simulation process. In order to validate the model, a serial of arcuate relaxing incisions (o.z. 6 mm) and limbal ones (10 mm) were simulated. One of the principal measurable biomechanical properties of the Cornea, which is the Corneal Hysteresis, was also simulated with this model. Results Regarding the simulation of arcuates and limbal incisions with the model, the obtained results were similar to those stated in different nomograms and surgical in vivo outcomes. The measure of Corneal Hysteresis was reproduced with this model obtaining similar results to measures in vivo performed with the Ocular Response Analyzer (REICHERT). The model can also be useful to simulate other surgical techniques like intraCorneal rings, LASIK or keratoplastia. This model is a first approach to a future one which can customize by reproducing a patient specific Corneal geometry and material properties. Conclusion The model was useful to reproduce several surgical techniques and properties measures and offers a lot of possibilities for predicting effects of future surgery techniques.
-
finite element simulation of arcuates for astigmatism correction
Journal of Biomechanics, 2008Co-Authors: Elena Lanchares, B Calvo, José Antonio Gómez Cristobal, Manuel DoblaréAbstract:In order to simulate the Corneal incisions used to correct astigmatism, a three-dimensional finite element model was generated from a simplified geometry of the anterior half of the ocular globe. A hyperelastic constitutive behavior was assumed for Cornea, Limbus and sclera, which are collagenous materials with a fiber structure. Due to the preferred orientations of the collagen fibrils, Corneal and limbal tissues were considered anisotropic, whereas the sclera was simplified to an isotropic one assuming that fibrils are randomly disposed. The reference configuration, which includes the initial strain distribution that balances the intraocular pressure, is obtained by an iterative process. Then the incisions are simulated. The final positions of the nodes belonging to the incised meridian and to the perpendicular one are fitted by both radii of curvature, which are used to calculate the optical power. The simulated incisions were those specified by Lindstrom's nomogram [Chu, Y., Hardten, D., Lindquist, T., Lindstrom, R., 2005. Astigmatic keratotomy. Duane's Ophthalmology. Lippincott Williams and Wilkins, Philadelphia] to achieve 1.5, 2.25, 3.0, 4.5 and 6.0 D of astigmatic change, using the next values for the parameters: length of 45°, 60° and 90°, an optical zone of 6 mm, single or paired incisions. The model gives results similar to those in Lindstrom's nomogram [Chu et al., 2005] and can be considered a useful tool to plan and simulate refractive surgery by predicting the outcomes of different sorts of incisions and to optimize the values for the parameters involved: depth, length, position.