Targeted administration into the suprachoroidal space using a microneedle for drug delivery to the posterior segment of the eye.

Purpose: This study seeks to determine the intraocular pharmacokinetics of molecules and particles injected into the suprachoroidal space of the rabbit eye in vivo using a hollow microneedle.

Methods: Suprachoroidal injections of fluorescein and fluorescently tagged dextrans (40 and 250 kDa), bevacizumab, and polymeric particles (20 nm to 10 μm in diameter) were performed using microneedles in New Zealand white rabbits. The fluorescence intensity within the eye was monitored in each animal using an ocular fluorophotometer to determine the distribution of the injected material in the eye over time as compared with intravitreal injection of fluorescein.

In vivo ocular fluorophotometry: delivery of fluoresceinated dextrans via transscleral diffusion in rabbits.

Purpose: To evaluate the transscleral delivery of fluoresceinated dextrans (FITC-D) with molecular mass up to 70 kDa to the rabbit posterior segment using sub-Tenon injections.

Methods: Eighteen NZW rabbits received a unilateral 200-μL injection of 2 mg/mL sodium fluorescein (NaF), 25 mg/mL 40-kDa FITC-D, or 25 mg/mL 70-kDa FITC-D, with (n = 9) or without (n = 9) immediate euthanatization. In live animals, fluorescence was measured in the retina/choroid and mid-vitreous by fluorophotometry, immediately after injection and after 4, 24, 48, and 72 hours.

Mucoadhesive microparticles in a rapidly dissolving tablet for sustained drug delivery to the eye.

Purpose: To test the hypothesis that mucoadhesive microparticles formulated in a rapidly dissolving tablet can achieve sustained drug delivery to the eye.

Methods: Mucoadhesive microparticles, smaller than 5 μm were fabricated with poly(lactic-co-glycolic acid) and poly(ethylene glycol) as a core material and mucoadhesion promoter, respectively, and encapsulated pilocarpine as a model drug. These microparticles were embedded in a poly(vinyl alcohol) matrix to form a dry tablet designed to reduce rapid clearance of the microparticles on initial application to the eye.

Trans-scleral permeability of Oregon green 488.

Purpose: The aim of this study was to determine the scleral permeability of a commercially available version of 2',7'-difluorofluorescein (OG) and compare it to that of sodium fluorescein (NaF).

Methods: Both in vitro and in vivo experiments were performed. For the ex vivo experiment, a Lucite block perfusion chamber with human donor sclera was used.

Mucoadhesive microdiscs engineered for ophthalmic drug delivery: effect of particle geometry and formulation on preocular residence time.

Purpose: To test the hypothesis that mucoadhesive microdiscs formulated in a rapidly dissolving tablet can increase preocular residence time.

Methods: Microparticles smaller than 10 mum in diameter were fabricated by emulsification with poly(lactic-co-glycolic acid) as a core material and, in some cases, poly(ethylene glycol) as a mucoadhesion promoter. To examine the effect of particle geometry, microparticles were also cut to have flat surfaces (i.

Pharmacokinetics of intraocular drug delivery of Oregon green 488-labeled triamcinolone by subtenon injection using ocular fluorophotometry in rabbit eyes.

Purpose: To evaluate the transscleral delivery of Oregon Green-labeled triamcinolone acetonide (OGTA) into the eye.

Methods: Ex vivo experiments were performed on rabbit sclera in a Lucite block perfusion chamber. Two hundred microliters OGTA (5 mg/mL) was placed on the outer surface of the sclera for 24 hours.

Targeting tissue factor-expressing tumor angiogenesis and tumors with EF24 conjugated to factor VIIa.

Tissue factor (TF) is aberrantly expressed on tumor vascular endothelial cells (VECs) and on cancer cells in many malignant tumors, but not on normal VECs, making it a promising target for cancer therapy. As a transmembrane receptor for coagulation factor VIIa (fVIIa), TF forms a high-affinity complex with its cognate ligand, which is subsequently internalized through receptor-mediated endocytosis. Accordingly, we developed a method for selectively delivering EF24, a potent synthetic curcumin analog, to TF-expressing tumor vasculature and tumors using fVIIa as a drug carrier.

Biomechanical and wound healing characteristics of corneas after excimer laser keratorefractive surgery: is there a difference between advanced surface ablation and sub-Bowman's keratomileusis?

Purpose: To describe the biomechanical and wound healing characteristics of corneas after excimer laser keratorefractive surgery.

Methods: Histologic, ultrastructural, and cohesive tensile strength evaluations were performed on 25 normal human corneal specimens, 206 uncomplicated LASIK specimens, 17 uncomplicated sub-Bowman's keratomileusis (SBK) specimens, 4 uncomplicated photorefractive keratectomy (PRK) specimens, 2 uncomplicated advanced surface ablation (ASA) specimens, 5 keratoconus specimens, 12 postoperative LASIK ectasia specimens, and 1 postoperative PRK ectasia specimen and compared to previously published studies.

Results: Histologic and ultrastructural studies of normal corneas showed significant differences in the direction of collagen fibrils and/or the degree of lamellar interweaving in Bowman's layer, the anterior third of the corneal stroma, the posterior two-thirds of the corneal stroma, and Descemet's membrane.

Depth-dependent cohesive tensile strength in human donor corneas: implications for refractive surgery.

Purpose: To determine the cohesive tensile strength throughout the stroma of normal human donor corneas and evaluate the relevance of these findings within the context of current excimer laser surgical techniques.

Methods: Twenty normal corneoscleral buttons from 11 donors were obtained from the Georgia Eye Bank. The corneas were cut into 3-mm strips, dissected at varying stromal depths, mechanically separated through the dissection plane using a motorized extensometer, and measured for cohesive tensile strength.

Review of corneal endothelial specular microscopy for FDA clinical trials of refractive procedures, surgical devices, and new intraocular drugs and solutions.

Specular microscopy can provide a noninvasive morphologic analysis of the corneal endothelial cell layer from subjects enrolled in clinical trials. The analysis provides a measure of the endothelial cell physiologic reserve from aging, ocular surgical procedures, pharmaceutical exposure, and general health of the corneal endothelium. The purpose of this review is to discuss normal and stressed endothelial cell morphology, the techniques for determining the morphology parameters, and clinical trial applications.

Corneal epithelial testing strategies for safety evaluation of ophthalmic formulations.

The toxicity of an ophthalmic formulation was tested both in vivo and in vitro. Initial tests on transformed human corneal epithelial (HCE-T) cells in monolayer cultures resulted in adverse effects on cell morphology. The adverse effects were unexpected since the formulation caused no damage to the cornea in vivo.

In vivo corneal epithelial permeability following treatment with prostaglandin analogs [correction of analoges] with or without benzalkonium chloride.

The effects of two intraocular pressure (IOP)-lowering agents, latanoprost with 0.02% benzylalkonium chloride (BAK) and travoprost Z without BAK, on corneal epithelial permeability, assessed by carboxyfluorescein uptake, were compared in a rabbit cornea model (n = 12). Loss of epithelial tight junctions was measured by ruthenium red uptake with transmission electron microscopy.

Coated microneedles for drug delivery to the eye.

Purpose: To test the hypothesis that coated microneedles can deliver drugs into the eye via intrascleral and intracorneal routes in a minimally invasive manner.

Methods: Solid metal microneedles measuring 500 to 750 microm in length were coated with model drugs, protein, and DNA; inserted into nonpreserved human cadaveric sclera; and imaged. Microneedles coated with sodium fluorescein were then inserted into rabbit cornea in vivo.

Pharmacokinetics of intraocular drug delivery by periocular injections using ocular fluorophotometry.

Purpose: To evaluate the pharmacokinetics of the periocular injections: posterior subtenon (PST), retrobulbar (RB), and subconjunctival (SC) injection.

Methods: Two sodium fluorescein (NaF) concentrations, 2.5 mg in 0.

Cohesive tensile strength of human LASIK wounds with histologic, ultrastructural, and clinical correlations.

Purpose: To measure the cohesive tensile strength of human LASIK corneal wounds.

Methods: Twenty-five human eye bank corneas from 13 donors that had LASIK were cut into 4-mm corneoscleral strips and dissected to expose the interface wound. Using a motorized pulling device, the force required to separate the wound was recorded.

Low incidence of iris pigmentation and eyelash changes in 2 randomized clinical trials with unoprostone isopropyl 0.15%.

Objective: To assess whether iris color and eyelash changes occur with the use of unoprostone for 2 years.

Design: The 2 clinical trials described herein were prospective, randomized, double-masked, active-controlled, parallel group, multicenter studies.

Participants: A total of 1131 patients with primary open-angle glaucoma or ocular hypertension participated in 2 clinical trials and received either unoprostone isopropyl 0.

The distribution of strain in the human cornea.

Experimental data on the mechanics of human cornea is meager and sometimes flawed. Moreover, questions regarding the correct material symmetry and the role of the fibrous microstructure are usually glossed over when mechanical models of the cornea and corneal shape changing procedures are presented. Accordingly, the deformation of 14 intact human corneas was measured for five pressures in the physiologic range (0, 5, 10, 25 and 45 cmH2O) by tracking small, self-adherent particles placed on their anterior surfaces.

Effect of tear lubricating solutions on in vivo corneal epithelial permeability.

Purpose: The rabbit corneal epithelial permeability was measured noninvasively following exposure to commercially available tear lubricating solutions.

Methods: The normal unanesthetized rabbit's corneal surface was either bathed in the tear lubricating solution for 5 min or received multiple applications of 2 drops per 30 min for 6 h for one or five days. The corneal epithelial permeability to carboxyfluorescein after a 5-min bath was measured with the Fluorotron Master.

Corneal endothelial damage by air bubbles during phacoemulsification.

Objective: To characterize the mechanism by which air bubbles damage the corneal endothelium during phacoemulsification.

Materials And Methods: A series of experiments was conducted to expose the corneal endothelium of New Zealand white rabbit and human eyes that were obtained from an eye bank to air under different conditions. Phacoemulsification at different power settings and irrigation with and without the introduction of air into the anterior chamber were performed.

The illuminated high contrast macular grid: a pilot study.

Background: Analysis of visual disturbances in the central 10 degrees provides valuable data for the low vision clinician. Amsler grid testing in the visually impaired can be poorly visible and it can be difficult to transcribe results. Automated perimeters will accurately map retinal defects, but the equipment is expensive and this technique is time consuming.

Noninvasive measurement of corneal epithelial permeability.

The Fluorotron Master fluorophotometer was used to measure the corneal epithelial permeability to carboxyfluorescein in the normal unanesthetized rabbit. This was related to the epithelial fluorescein staining grade as assessed with a slit lamp. The carboxyfluorescein concentration in the cornea was measured at 3, 60 and 120 min after bathing the cornea in 2.

Corneal wound healing strength with topical antiinflammatory drugs.

The objective of this study was to compare the force required to separate corneal wounds after topical applications of nonsteroidal antiinflammatory drugs (NSAIDs) or corticosteroids. Bilateral central 8-mm long corneal full-thickness incisions in 50 NZW rabbits were closed with five interrupted 10-0 nylon sutures. There were four paired-eye groups: (a) control/control, (b) control/diclofenac sodium (0.

Topographic evaluation of toric soft contact lens correction.

The anterior surface of the eye provides the greatest refracting surface to the optical system of the eye because of the large difference in refractive index between air and tissue. When a contact lens is placed on the eye, its anterior surface becomes the greatest refracting surface. Toric soft contact lenses have been designed to neutralize ocular astigmatism.

Nicotine on the revascularization of bone graft. An experimental study in rabbits.

Study Design: In 24 rabbits, the authors transplanted autologous cancellous bone to the anterior chamber of the eye. Half of the rabbits received nicotine and half received placebo (albumin) from mini-osmotic pumps that were implanted subcutaneously. Revascularization of the bone graft was evaluated postoperatively using ophthalmology slit-lamp and fluorescein angiography, and after sacrifice using microvascular silicone injection and histology.

Surface topography of soft contact lenses for neutralizing corneal astigmatism.

We compared the surface topography of 38 soft contact lenses in situ to the corneal topography of 17 patients. The analyzed lenses consisted of patients' spherical and toric lenses as well as additional spherical lenses of various thicknesses. Thirteen brands of contact lenses were worn; corneal astigmatism ranged from 0.