Valerie Jallet

Novel synthetic meshwork for glaucoma treatment. I. Design and preliminary in vitro and in vivo evaluation of various expanded poly(tetrafluoroethylene) materials.

A novel drainage implant for glaucoma filtering surgery (MESH) is proposed. After various expanded poly(tetrafluoroethylene) (e-PFTE) materials were evaluated, the feasibility and the short-term safety of the technique were assessed in this first pilot study in the rabbit. The porous structure and the in vitro resistance to aqueous flow of seven different e-PTFE membranes (5-80 microm average pore size) were compared. Eight Dutch pigmented rabbits were implanted with the T-shaped MESH implants made from either 20- or 50-microm average pore size e-PTFE membranes. Clinical examination, intraocular pressure (IOP) measurements, and histology analyses were performed over a period of 3 months. The contralateral nonoperated eyes served as controls. MESH implantation took less than 7 min. No postoperative hypotony, migration, or extrusion of the implant and no intraocular inflammation or infection occurred. A significant IOP reduction in the implanted eyes was obtained past postoperative day 21 with the 20-microm material implant. The drainage efficacy was correlated with the degree of colonization of the porous materials and the inner spacing of the implant as observed by histology. With a filtering patency 3 times longer than conventional trabeculectomy and laser sclerectomy, MESH surgery is a promising technique for glaucoma treatment. Further studies are underway to enhance the device efficacy and understand the mechanism of filtration.

Deep sclerectomy with and without implant: an in-vivo comparative study

Purpose: Establish the effects of pre-Descemetic sclero- keratectomy, a new nonpenetrating Deep-Sclerectomy filtration procedure, with and without crosslinked sodium hyaluronic acid (SKgel) implant in the rabbit animal model. Materials and Methods: Ten adult NZW rabbits had surgery only (group A) and 15 other had surgery and a crosslinked sodium hyaluronate implant inserted under the scleral flap (group B). Weekly intraocular pressure (IOP), outflow facility, and central and peripheral corneal thicknesses were measured in both the operated and the contralateral eye over a period of five months in Group A and six months in Group B. Results: IOP was consistently lower until POD 21 for Group A and POD 161 for Group B, respectively (P less than 0.05). Outflow facility was significantly higher than control eyes until POD 14 in Group A and until POD 84 in Group B. Peripheral corneal thickness returned to normal by POD 14 in Group A and POD 28 in Group B. By POD 35, there was no statistical significance between both groups in the mean of peripheral corneal thickness. Conclusion: Pre-Descemetic Sclero-Keratectomy with crosslinked sodium hyaluronate implant is effective in reducing IOP and safe operation in rabbit eyes.

Assessment of surface concentrations in resorbable ocular implants: controlled drug delivery devices for 5-fluorouracil (5-FU)

The antineoplastic drug 5-fluorouracil (5-fluoro- 2,4,(1H,3H)-pyrimidinedione; 5-FU) has been used to control proliferation of penetrating fibroblasts and to prevent channel closure following glaucoma filtration surgery (trabeculectomy) or laser sclerectomy. Because of the toxicity of the drug, administration of low dosages slowly over time, at the site of the desired treatment, is indicated for optimum efficacy. Repeated injections of low dosages of the drug represent an undesirable intervention and may also result in unwanted toxicity to the corneal epithelium. A suitable biocompatible and resorbable polymer matrix composed of a poly (D,L-lactic-co-glycolic acid: PLGA) has been admixed with varying amounts of 5-FU and cast as shapes suitable for intracorneal implantation. Slow biodegradation of this polymer over a one to two week period has been shown to result in an acceptably slow drug release mechanism. An issue arising during the clinical evaluation of the efficacy of this drug delivery system was how best to quantify the concentration of 5-FU and its distribution spatially in the solid implant. FT-IR and FT-Raman spectroscopies distinguishes between the drug and the polymer matrix and were used to differentiate and quantitate the 5-FU concentration of the implants.

Scattering of ocular tissues and polymers

Ocular tissues are mainly made up from conjunctive fibers on the basis of collagen. The way they are arranged as well as the proportion of water contained in the tissues determines their transparency. As example the fibers in the sclera have diameters between 30 and 300 nm and are arranged in ribbon-like fiber bundles (15 microns thick and 140 to 150 microns wide) that cross each other in all directions [1]. Both different diameters and interlaced structure lead to a tissue displaying scattering properties. By opposition the cornea scatters visible light in a much lower amount, mainly because it is up from fibers having diameters varying only between 19 and 34 microns and that are organized in a parallel fashion within layers. Such a structure is of primary importance when objects have to be imaged through such tissues because scattering results in a blur of the image obtained. Therefore, any irregular change in the structure due to anarchical growth or in diameter as it may be the case with ageing of the crystalline lens results in a loss of visual acuity. The use of biocompatible materials has tremendously increased in ophthalmology during the last years. PMMA still represents the majority of the intraocular lenses replacing the refractive power of the crystalline lens. Viscoelastic materials are currently utilized in the anterior chamber and perfluorocarbons or other polymers like polydimethylsiloxanes (PDMS) are used as vitreous substitutes. The physical properties of such materials should be similar to those of the tissue they replace. Consequently, whenever possible flexible materials that mimic ocular tissues are developed in order to minimize local stress and tissue deformation. Among them, gels that consist of a network crosslinked in a balanced salt solution (BSS) have also been tested as intracorneal implants for GIAK (gel injection adjustable keratoplasty), a technique designed to correct myopia [2]. Because the number of intermolecular bonds per linear chain governs the rigidity of the material, various collagenous tissues can be mimicked by controlling both concentration of the network and the degree of crosslinking. However, when such materials are implanted within the optical path of the eye, their optical properties should be scrutinized. A high transparency is necessary in the visible part of the spectrum (450-700nm), associated with a high absorption in the UV and the deep blue part (400-450nm) for protection of the retina and the crystalline lens. In addition, scattering should also be minimized to avoid loss of visual acuity. Therefore, apart from an accurate shape and refractive index, the surface quality and the homogeneity of the implants have also to be as high as possible. The purpose of this study was to compare the scattering of such materials to that of ocular structures.