Development of No-Rejection Aqueous Humor Pressure Control Membrane in The Eyeball for Glaucoma Implant Devices

The inner porous part of the PTFE [poly-tetrafluoroethylene] membrane was substituted with a hydrophilic group using irradiation by an ArF laser. Water was employed for a defluorination agent in order to inhibit rejection. The membrane was developed that automatically pumps out water when the pressure is raised above a fixed value. The increased intraocular pressure with aqueous outflow failure causes glaucoma. In healthy humans intraocular pressure is maintained at a normal physiological level of between 8 to 18 mmHg. When the pressure exceeds 21 mmHg, a diagnostic of glaucoma may be predicted. We designed a new type of membrane to pump the aqueous humor and regulate its outflow. The membrane has gained characteristics of aqueous humor penetration by substituting a part of a hydrophobic group that exists inside the porous PTFE with the hydrophilic group. Furthermore our previous studies have found that B, Al and H atoms are effective for defluorination of atoms from fluorocarbon. In this study three kinds of reaction liquid containing B, Al and H respectively were used. By this defluorination reaction B and Al atoms were better than H atoms. We prepared a boric acid water solution (B(OH)3), nitro aluminate water solution (Al(NO3)3) and water (H2O) as chemical compounds for defluorination and OH substitution. When ethyl alcohol is dropped on the porous PTFE, it penetrates into inner porous PTFE easily. When the three kinds of chemical compound water solutions are dropped onto the porous PTFE membrane, the solution is trapped up to the inner side of porous PTFE. When each sample with hydrophilic property treatment was implanted into rabbits' eyes and its biocompatibility was tested, some samples using Al and B atoms for defluorination have shown the rejection reaction called neoplasm blood vessel. However, the other samples using water as the reaction liquid have shown no rejection

Reduction of corneal edema in endotoxin-induced uveitis after application of L-NAME as nitric oxide synthase inhibitor in rats by iontophoresis.

PURPOSE: To investigate the involvement of the cornea during endotoxin-induced uveitis (EIU) in the rat and the effect of Ngamma-nitro-L-arginine methyl ester (L-NAME) as nitric oxide synthase (NOS) inhibitor, administered by iontophoresis. METHODS: EIU was induced in Lewis rats that were killed at 8 and 16 hours after lipopolysaccharide (LPS) injection. The severity of uveitis was evaluated clinically at 16 hours, and nitrite levels were evaluated in the aqueous humor at 8 hours. Corneal thickness was measured, 16 hours after LPS injection, on histologic sections using an image analyzer. Transmission electron microscopy (TEM) was used for fine analysis of the cornea. Transcorneoscleral iontophoresis of L-NAME (100 mM) was performed either at LPS injection or at 1 and 2 hours after LPS injection. RESULTS: At 16 hours after LPS injection, mean corneal thickness was 153.7+/-5.58 microm in the group of rats injected with LPS (n=8) compared with 126.89+/-11.11 microm in the saline-injected rats (n=8) (P < 0.01). TEM showed stromal edema and signs of damage in the endothelial and epithelial layers. In the group of rats treated by three successive iontophoreses of L-NAME (n=8), corneal thickness was 125.24+/-10.36 microm compared with 146.76+/-7.52 microm in the group of rats treated with iontophoresis of saline (n=8), (P=0.015). TEM observation showed a reduction of stromal edema and a normal endothelium. Nitrite levels in the aqueous humor were significantly reduced at 8 hours by L-NAME treatment (P=0.03). No effect on corneal edema was observed after a single iontophoresis of L-NAME at LPS injection (P=0.19). Iontophoresis of saline by itself induced no change in corneal thickness nor in TEM structure analysis compared with normal rats. CONCLUSIONS: Corneal edema is observed during EIU. This edema is significantly reduced by three successive iontophoreses of L-NAME, which partially inhibited the inflammation. A role of nitric oxide in the corneal endothelium functions may explain the antiedematous effect of L-NAME

High-resolution optical coherence tomography-guided donor tissue preparation for descemet membrane endothelial keratoplasty using the reverse big bubble technique.

The aim of this study was to assess the feasibility of high-resolution spectral domain optical coherence tomography (HR-SDOCT) to guide donor tissue preparation in Descemet membrane endothelial keratoplasty using the reverse big bubble technique. Three corneoscleral discs were included in this ex vivo experimental study. A 27-G cannula was introduced into each cornea at the periphery by 3 different surgeons. Each surgeon attempted to achieve the ideal depth (pre-Descemetic plane) of the tip of the cannula for air injection to produce the reverse big bubble to separate the Descemet membrane (DM) from the posterior stroma. A supine optical coherence tomography system built at the Ophthalmic Biophysics Center of the Bascom Palmer Eye Institute was used to estimate in real-time the depth reached by the tip of the cannula in the posterior stroma during tissue preparation. After air injection, 1 successful big bubble was obtained, while each of the other corneoscleral discs had intrastromal emphysema and DM perforation. On HR-SDOCT evaluations, artifacts were noticed at the tip of the cannula. The successful big bubble demonstrated the separation of the DM and the stroma without intrastromal hyperreflectivity. Emphysema was visualized on the HR-SDOCT as a hyperdense intrastromal area shadowing the posterior structures of the anterior chamber. The HR-SDOCT-guided reverse big bubble technique may be a useful method to prepare donor tissue in Descemet membrane endothelial keratoplasty. Further improvements in high-resolution optical coherence tomography technology are needed this promising technique

Transscleral Coulomb-controlled iontophoresis of methylprednisolone into the rabbit eye: influence of duration of treatment, current intensity and drug concentration on ocular tissue and fluid levels.

The major problems associated with the use of corticosteroids for the treatment of ocular diseases are their poor intraocular penetration to the posterior segment when administered locally and their secondary side effects when given systemically. To circumvent these problems more efficient methods and techniques of local delivery are being developed. The purposes of this study were: (1) to investigate the pharmacokinetics of intraocular penetration of hemisuccinate methyl prednisolone (HMP) after its delivery using the transscleral Coulomb controlled iontophoresis (CCI) system applied to the eye or after intravenous (i.v.) injection in the rabbit, (2) to test the safety of the CCI system for the treated eyes and (3) to compare the pharmacokinetic profiles of HMP intraocular distribution after CCI delivery to i.v. injection. For each parameter evaluated, six rabbit eyes were used. For the CCI system, two concentrations of HMP (62.5 and 150mg ml(-1)), various intensities of current and duration of treatment were analyzed. In rabbits serving as controls the HMP was infused in the CCI device but without applied electric current. For the i.v. delivery, HMP at 10mg kg(-1)as a 62.5mg ml(-1)solution was used. The rabbits were observed clinically for evidence of ocular toxicity. At various time points after the administration of drug, rabbits were killed and intraocular fluids and tissues were sampled for methylprednisolone (MP) concentrations by high pressure liquid chromatography (HPLC). Histology examinations were performed on six eyes of each group. Among groups that received CCI, the concentrations of MP increased in all ocular tissues and fluids in relation to the intensities of current used (0.4, 1.0 and 2.0mA/0.5cm(2)) and its duration (4 and 10min). Sustained and highest levels of MP were achieved in the choroid and the retina of rabbit eyes treated with the highest current and 10min duration of CCI. No clinical toxicity or histological lesions were observed following CCI. Negligible amounts of MP were found in ocular tissues in the CCI control group without application of current. Compared to i.v. administration, CCI achieved higher and more sustained tissue concentrations with negligible systemic absorption. These data demonstrate that high levels of MP can be safely achieved in intraocular tissues and fluids of the rabbit eye, using CCI. With this system, intraocular tissues levels of MP are higher than those achieved after i.v. injection. Furthermore, if needed, the drug levels achieved with CCI can be modulated as a function of current intensity and duration of treatment. CCI could therefore be used as an alternative method for the delivery of high levels of MP to the intraocular tissues of both the anterior and posterior segments

Methylprednisolone concentrations in the vitreous and the serum after pulse therapy.

PURPOSE: Intravenous (i.v.) pulse of corticosteroids has been used to treat severe eye inflammation from different origins. Whether such large doses result in vitreous levels that differ either in magnitude or duration from more conventional corticotherapy remain unsolved issues. The authors therefore determined levels of methylprednisolone hemisuccinate and methylprednisolone in the vitreous and serum of patients at different times after a single i.v. perfusion of methylprednisolone hemisuccinate. METHODS: Fifty patients scheduled for a first vitrectomy received an i.v. injection of 500 mg hemisuccinate methylprednisolone at different times before surgery (from 15-24 hours). Patients were divided into two groups: those with (n = 21) and without (n = 29) retinal detachment (RD). Pure vitreous samples were analyzed by high-pressure liquid chromatography. RESULTS: Both the ester and the nonester methylprednisolone forms were sampled in the vitreous, showing a slower rate of hydrolysis compared to the serum. On average, the highest concentration of total methylprednisolone in the vitreous was found at 2.5 hours and rapidly decreased for the group of patients with RD. In the group of patients without RD, the highest concentration was reached at 6 hours and then slowly decreased. The antiinflammatory potency in the nondetached retina eyes was approximately 500 times more than in the physiologic vitreous, but despite the route of administration (i.v. or oral), only 1/10 of the corticosteroid serum concentration was measured in the vitreous. CONCLUSION: High concentration of methylprednisolone is achieved by i.v. pulse therapy without changing the kinetic of entry in the vitreous of nondetached retina eyes when compared to conventional oral corticotherapy. Hydrolysis occurs in the vitreous resulting in high rate of active form. Pulse therapy could be considered in cases of severe ocular inflammation involving the posterior segment of the eye