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H F Edelhauser

Publications and source records attributed to H F Edelhauser.

At least 19 recordsLinked to original sources
PubMed2003

Ocular surgical pharmacology: corneal endothelial safety and toxicity.

The purpose of this review is to discuss the recently published literature related to corneal endothelial toxicity and safety. We discuss postoperative complications, such as toxic endothelial cell destruction syndrome and toxic anterior segment syndrome, that cause significant injury to the patient and anxiety to the physician. Additionally, we review recent papers related to intraocular medications, preservatives, and devices, including antibiotics, anesthetics, viscoelastics, and enzymatic sterilization detergents, that have potentially toxic effects on the corneal endothelium.

Corneal Diseases↗
PubMed2001

Transscleral drug delivery for posterior segment disease.

Exciting new treatments are being developed for retinal degenerations and posterior segment eye disease. The successful treatment of these visually devastating diseases will likely require delivering effective doses of pharmacologic agents to the posterior segment, possibly in conjunction with surgical or genetic interventions. Currently, the treatment of diseases affecting the posterior segment is limited by the difficulty in delivering effective doses of drugs to target tissues in the posterior vitreous, retina or choroid. This review summarizes recent laboratory and clinical studies that indicate that transscleral delivery of therapeutic solutes might be an effective means of achieving therapeutic concentrations of these agents in the posterior eye.

Animals↗
PubMed2001

Effects of laser in situ keratomileusis (LASIK) on the corneal endothelium 3 years postoperatively.

PURPOSE: To investigate the effects of laser in situ keratomileusis (LASIK) on the corneal endothelium 3 years postoperatively. METHODS: Patients who were subjects of a previous prospective study (Am J Ophthalmol 125:465-471, (April) 1998) were contacted for a follow-up analysis of the central corneal endothelium. Noncontact specular microscopy was performed 35 to 37 months after LASIK on 52 eyes of 27 patients of the original cohort of 98 eyes of 65 patients and six eyes of three patients who were previously lost to follow-up after their initial post-LASIK evaluation. Patient age ranged from 29 to 66 years at the time of the original LASIK procedure. Attempted corrections ranged from 2.25 to 14.5 diopters of myopia, giving theoretical ablation depths of 182 to 332 microm below the corneal surface. Forty-eight eyes (83%) had a history of preoperative contact lens use (3 to 33 years). Central endothelial cell density, coefficient of variation of cell size, and percent of hexagonal cells were analyzed using 72 to 152 cells from each image. Multivariate analysis was used to search for factors that might predict changes in cell density, coefficient of variation, and percent of hexagonal cells. RESULTS: The mean +/- SD preoperative cell density was 2,498 +/- 354 cells per mm(2), the mean coefficient of variation was 0.36 +/- 0.07, and the percent of hexagonal cells was 58 +/- 6. Three years after surgery there was no statistically significant change in the mean endothelial cell density (2,489 +/- 335 cells per mm(2); P = 0.88, paired t test) or the percent of hexagonal cells (60 +/- 7; P = 0.14, paired t test). The mean coefficient of variation was significantly lower postoperatively (0.32 +/- 0.04; P = 0.0006, paired t test); a repeated measures analysis showed that this significant improvement could not be explained by cessation of contact lens wear after LASIK (P = 0.34). Multivariate analysis did not identify any factors that were predictive of change in cell density, coefficient of variation, and percent of hexagonal cells. CONCLUSIONS: Laser in situ keratomileusis for the correction of 2.25 to 14.5 diopters of myopia had no significant effect on central corneal endothelial cell density or the percent of hexagonal cells 3 years after surgery. The coefficient of variation of cell size improved significantly 3 years after surgery.

Adult↗
PubMed2001

Acute corneal endothelial changes after laser in situ keratomileusis.

PURPOSE: To report the acute effects of laser in situ keratomileusis (LASIK) on the corneal endothelium. METHODS: Twenty eyes of 10 consecutive patients (mean age, 38.1 +/- 10.84 years) underwent bilateral simultaneous LASIK for myopic astigmatism (spherical equivalent ranging from -1.75 to -7.13 diopters) without any complications. Each eye was evaluated by slit-lamp biomicroscopy and noncontact specular microscopy preoperatively, within 15 minutes after LASIK and 1 day after surgery. Specular microscopy images were then analyzed to calculate endothelial cell density (ECD), coefficient of variation (CV) of cell size, and percentage of hexagonal cells. RESULTS: All corneas demonstrated marked alterations in endothelial cell morphology by slit-lamp biomicroscopy within 15 minutes after surgery that resolved by the first postoperative day. Central corneal endothelial analysis by noncontact specular microscopy confirmed pleomorphism with definite loss of hexagonality. Mean ECD was calculated to be 2,816.3 +/- 286.02 cells/mm(2) preoperatively, 2,750.85 +/- 327.95 cells/mm(2) on day 0 (p = 0.395), and 2,810.55 +/- 218.48 cells/mm(2) on day 1 (p = 0.461). Mean CV was 32.65 +/- 7.29 preoperatively, 34.4 +/- 6.19 on day 0 (p = 0.412), and 30.9 +/- 5.54 on day 1 (p = 0.067). Mean percentage of hexagonal cells was 63.35 +/- 10.76 preoperatively, 47.55 +/- 9.69 on day 0 (p = 0.000009), and 60 +/- 9.3 on day 1 (p = 0.00003). CONCLUSION: Qualitative and quantitative changes in endothelial cell morphology (i.e., decreased endothelial cell hexagonality) demonstrate that LASIK does induce an acute effect on the corneal endothelium that may represent transient endothelial cell edema.

Acute Disease↗
PubMed2001

A simple corneal perfusion chamber for drug penetration and toxicity studies.

AIMS: Corneal perfusion chambers are important tools in the development and assessment of ophthalmic drugs. The aim of this study was to design and test a modified perfusion chamber suitable for topical application of drugs to isolated corneoscleral preparations, and which allowed continuous monitoring of endothelial cell function. METHODS: A polycarbonate and stainless steel perfusion chamber was designed to clamp corneas in a horizontal plane suitable for topical drug delivery. Endothelial cell function was assessed by ultrasonic pachymetry and specular microscopy during perfusion. Epithelial barrier function was assessed by penetration of fluorescein. Leakage was examined by measuring penetration of a large protein, IgG. Tissue architecture after perfusion was examined by conventional histology. RESULTS: Corneas maintained a functionally and morphologically intact endothelial monolayer during perfusion periods of up to 14 hours. The epithelial barrier function was well preserved. The tissue clamp sealed the preparation effectively against leakage of macromolecules. CONCLUSION: The new chamber device forms a reliable tool for in vitro drug penetration and toxicity studies in isolated perfused corneoscleral tissue.

Animals↗
PubMed2001

The expression of functional LPS receptor proteins CD14 and toll-like receptor 4 in human corneal cells.

PURPOSE: Gram-negative bacterial infections of the eye can lead to corneal bacterial keratitis, visual impairment, and blindness. Many of these pathologic changes may be mediated by bacterially derived products such as lipopolysaccharide (LPS). In this investigation, it has been established for the first time that human corneal cells are capable of expressing the functional LPS receptor complex proteins, CD14 and Toll-like receptor 4 (TLR4). METHODS: CD14 and TLR4 mRNA expression in human corneal cells was determined by RT-PCR and Northern blot analysis, and cell surface expression of these proteins was measured by flow cytometry. LPS-mediated corneal cell activation was determined by measuring intracellular calcium mobilization. Cellular cytokine and chemokine secretion in response to LPS was measured by ELISA. The expression and localization of CD14 in whole human cornea was determined by immunohistochemistry. RESULTS: Human corneal epithelial, stromal, and endothelial cells expressed CD14 mRNA and cell surface CD14. LPS binding to cornea CD14 resulted in a rapid intracellular calcium response and the secretion of multiple proinflammatory cytokines and chemokines. CD14 mRNA expression in corneal epithelial cells was upregulated by LPS. In addition to CD14, corneal epithelial cells expressed the functional LPS receptor-signaling protein TLR4, which was also augmented by LPS. CONCLUSIONS: The cornea expresses functional CD14 and TLR4 LPS receptor proteins. Understanding the function and biology of the corneal LPS receptor complex may lead to novel therapies for the management of ocular Gram-negative bacterial infections.

Base Sequence↗
PubMed2000

Unexpected corneal endothelial cell decompensation after intraocular surgery with instruments sterilized by plasma gas.

PURPOSE: Ten cases of unexpected corneal endothelial cell decompensation occurring after routine intraocular surgery using instruments sterilized with a new plasma gas protocol are described. DESIGN: A retrospective observational case series with 1 year of follow-up was conducted. RESULTS: All patients had corneal decompensation and nonreactive pupils after surgery. Six patients required penetrating keratoplasty. Three patients partially recovered pupillary function. Visual acuity at 1 year ranged from 20/20 to hand motion (HM). One patient with an anterior chamber intraocular lens (ACIOL) experienced optic atrophy and HM vision despite resolution of corneal edema. CONCLUSIONS: Toxic corneal endothelial cell destruction syndrome was associated with the introduction of plasma gas sterilization protocols.

Adult↗
PubMed2000

The resiliency of the corneal endothelium to refractive and intraocular surgery.

PURPOSE: To describe stress factors (phenylephrine and contact lenses) from the corneal epithelium that can affect the corneal endothelium, and to describe the effects of refractive and intraocular surgery on the corneal endothelial structure and function. METHODS: Significant clinical and experimental publications are reviewed and recent experiments conducted in the author's laboratory to describe the corneal endothelial stresses. RESULTS: The corneal epithelium serves as a barrier to topical phenylephrine (2.5-10%). In a compromised epithelium, topical phenylephrine will cause drug-induced stromal edema and endothelial vacuolization. Contact lenses are capable of stimulating the epithelial arachidonic acid cascade to release 12(R)hydroxyeicosatetraenoic acid (12(R)HETE) and 8(R)hydroxy-hexadecatrienoic acid (8(R)HHDTrE) to cause endothelial Na+/K+ adenosine triphosphatase (ATPase)-inhibition and polymegethism. Specular microscopy of the corneal endothelial cells after refractive surgery (photorefractive keratectomy [PRK], laser in situ keratomileusis [LASIK], intrastromal rings [INTACs]) has shown that there is minimal effect. However, laser ablation of the stroma within 200 microm of the corneal endothelium will result in endothelial cell structural changes and the formation of the amorphous substance deposited onto Descemet's membrane. Phacoemulsification with a high flow of the irrigation solution can alter the endothelial surface glycoprotein layer. Lidocaine hydrochloride (1%) used as intracameral anesthesia readily diffuses through the corneal endothelium, resulting in stromal uptake and endothelial cell swelling. With phacoemulsification, however, the washout of lidocaine from the cornea (T1/2, 5 minutes) and iris (T1/2, 9 minutes) occurs quickly. Corneal endothelial wound healing after keratoplasty occurs in the following sequence: migration of endothelial cells, development of tight junctions, and the formation of Na+/K+ ATPase pump sites. CONCLUSIONS: Corneal endothelial resiliency is due to the increased peripheral endothelial cell number for migration, the ability of endothelial cells to form tight junctions to maintain the endothelial barrier, the increase in endothelial Na+/K+ ATPase pump sites under stress, and the ability of the corneal endothelial cells to shift their metabolism of glucose to the hexose monophosphate shunt for the production of nicotinamide adenine dinucleotide phosphate (NADPH) and membrane repair. All of these factors are important, along with the aqueous humor sodium concentration, which establishes the osmotic gradient for corneal deturgescence and transparency.

Adrenergic alpha-Agonists↗
PubMed2000

The mucinous layer of corneal endothelial cells.

PURPOSE: The goal of this study was to characterize the morphology of the mucinous layer on rabbit, bovine, owl, and human corneal endothelial cells. METHODS: Corneoscleral buttons were fixed using cetylpyridinium chloride to stabilize "mucus" and the tissue was prepared for transmission electron microscopy. Photomicrographs were measured to determine the thickness of the endothelial and epithelial mucinous layer in the central cornea. RESULTS: The endothelial mucinous layer was seen as a nearly uniform electrodense region on the apical aspect of the endothelium. It was found to be 0.9 microm, 0.9 microm, 0.9 microm, and 0.5 microm thick in rabbit, bovine, owl, and human, respectively. The owl endothelium had an additional less electrodense layer with a granular appearance and a thickness of about 200 microm. The mucinous layer on the epithelium was similar in appearance to that on the endothelium and across species. CONCLUSIONS: The morphologic similarity of the endothelial and epithelial mucinous layers is a serendipitous finding that should prove valuable in experimental design. Ultimately, it is hoped that studies of the posterior corneal surface will deepen our knowledge of endothelial protection.

Adult↗
PubMed1999

Intracameral anesthesia: in vitro iris and corneal uptake and washout of 1% lidocaine hydrochloride.

OBJECTIVES: To characterize the uptake, washout, and metabolism of lidocaine hydrochloride in the iris/ciliary body and cornea. METHODS: Iris/ciliary body uptake of lidocaine hydrochloride was measured by incubating human and rabbit irides in radiolabeled carbon 14-1% lidocaine hydrochloride for 2 to 60 minutes. Washout was determined by incubating the iris in 14C-1% lidocaine hydrochloride for 5 minutes and transferring the iris to a series of wells. The wells contained a common intraocular irrigating solution of essential ions, glucose, and glutathione buffered with bicarbonate (an enriched balanced salt solution [BSS PLUS]), which is similar to aqueous humor. Corneal uptake was measured by exposing the endothelial surface to 14C-1% lidocaine hydrochloride for 5 or 15 minutes. Corneal washout was performed after 5-minute exposure to 14C-1% lidocaine hydrochloride using a 2-chambered diffusion apparatus. Samples of the iris, cornea, and BSS PLUS washout solution were analyzed by high-performance liquid chromatography and liquid scintillation spectrometry. RESULTS: In vitro iris/ciliary body uptake of 14C-1% lidocaine hydrochloride follows a logarithmic curve, with 50% to 60% of maximum lidocaine hydrochloride uptake present at 5 minutes. There was no difference in uptake between human, albino rabbit, and pigmented rabbit irides. Washout of lidocaine from the iris occurs with a halflife of 8 to 9 minutes. Corneal uptake of lidocaine was greater after incubation for 15 vs. 5 minutes. The washout of lidocaine from the cornea had a half-life of 5 minutes. Results of high-performance liquid chromatography confirmed that there were no metabolites or breakdown products in the iris, cornea, or washout solution. CONCLUSIONS: Lidocaine is taken up quickly by the iris/ ciliary body and cornea and rapidly removed from these tissues after BSS PLUS washout. Irrigation during phacoemulsification seems to limit lidocaine exposure to the ocular tissues, resulting in a short duration of anesthesia. Lidocaine is not metabolized or broken down by the iris or cornea during this short period.

Anesthesia, Local↗
PubMed1999

Comparison of preservative-free bupivacaine vs. lidocaine for intracameral anesthesia: a randomized clinical trial and in vitro analysis.

PURPOSE: To determine whether intracameral bupivacaine hydrochloride 0.5% is as effective as lidocaine hydrochloride 1.0% in controlling discomfort of patients during phacoemulsification and posterior chamber intraocular lens implantation. In rabbits, corneal endothelial cell function, ultrastructure, and viability were evaluated after in vitro perfusion of bupivacaine 0.5%. METHODS: In a double-masked, controlled trial, 48 eyes of 48 patients with uncomplicated age-related cataract were randomly assigned to receive bupivacaine 0.5% or lidocaine 1.0% intracamerally before phacoemulsification with a posterior chamber intraocular lens. Outcome measures such as pain, visual acuity, amount of sedation, length of surgery, pupil size, intraocular pressure, corneal clarity, and anterior chamber reaction were compared. In laboratory studies, paired rabbit corneas were evaluated by endothelial cell perfusion with either bupivacaine 0.5%, bupivacaine 0.5% and glutathione bicarbonate Ringer solution in a 1:1 ratio or bupivacaine 0.5% buffered to a pH of 7.0. The paired control corneas were perfused with glutathione bicarbonate Ringer solution and rates of corneal swelling were determined. Cell ultrastructure and viability were also evaluated. RESULTS: In the randomized trial, there was no significant difference in the pain patients had during surgery or in the early or late postoperative period. No statistically significant difference was seen between the two groups in terms of pupil size, intraocular pressure, corneal edema, anterior chamber reaction, or visual acuity immediately after the operation or on postoperative day 1. Paired rabbit corneas perfused with bupivacaine 0.5% and bupivacaine 0.5% buffered to a pH of 7.0 swelled significantly (P<.001, P = .009, respectively), and had corneal endothelial cell damage. Dilution of the bupivacaine 1:1 with glutathione bicarbonate Ringer solution prevented corneal edema and damage to the corneal endothelium. Endothelial cell viability was also decreased after perfusion of bupivacaine 0.5% (P<.001). CONCLUSIONS: Clinically, bupivacaine 0.5% is as effective as lidocaine 1.0% for anesthesia during phacoemulsification and posterior chamber intraocular lens implantation. However, in vitro perfusion of bupivacaine 0.5% damaged the corneal endothelium of rabbits except when the drug was diluted 1:1 with glutathione bicarbonate Ringer solution. Surgeons who use 0.2 to 0.5 ml of intracameral bupivacaine 0.5% should be aware of its potential to cause endothelial cell damage because of its lipid solubility. The bupivacaine 0.5% should be diluted at least 1:1 with balanced salt solution before intracameral injection, followed immediately by phacoemulsification. The surgeon should ensure that the bupivacaine 0.5% is nonpreserved and packaged in single-use vials or flip-top containers.

Aged↗
PubMed1999

Toxicity of ocular surgical solutions.

Intraocular medications, solutions, and instruments are an integral component of intraocular surgery. The ionic composition, pH, and osmolality should approximate aqueous humor to prevent damage to the corneal endothelium. Intraocular medications should be evaluated for their intrinsic properties and presence of vehicles or preservatives. Many new cleaning procedures and promising new intraocular drugs are likely to be introduced in the future. The responsibility of ocular surgeons is to protect their patients from drug-, solution-, or instrument-related toxicity.

Eye↗
PubMed1999

The effect of intraocular pressure on human and rabbit scleral permeability.

PURPOSE: The purpose of this study was to evaluate the effects of intraocular pressure on the permeability of human and rabbit sclera to water, dexamethasone, and carboxyfluorescein. METHODS: Scleral sections excised from moist-chamber-stored human globes or eyes obtained from euthanatized New Zealand White rabbits were mounted in a perfusion chamber that can create a transscleral pressure that simulates an intraocular pressure. A small depot of drug (100 microl) was added to the episcleral surface while perfusing an irrigating solution slowly across the choroidal side. The perfusate was collected and scleral permeability calculated. Experiments were performed at 0, 15, 30, and 60 mm Hg for each compound in human and rabbit tissue. RESULTS: Analysis of variance showed a significant effect of intraocular pressure on both human and rabbit scleral permeability. Human scleral permeability was decreased by as much as a factor of two for water (P = 0.0004), dexamethasone (P<0.0001), and carboxyfluorescein (P = 0.0064) at elevated intraocular pressures. Rabbit scleral permeability was similarly affected by elevated intraocular pressure for water (P = 0.0039), dexamethasone (P = 0.0001), and carboxyfluorescein (P = 0.0016). CONCLUSIONS: This study shows that simulated intraocular pressure ranging from 15 to 60 mm Hg can decrease scleral permeability to small molecules by one half when compared with the sclera with no pressure applied.

Animals↗
PubMed1998

Storage of human corneas in dextran and chondroitin sulfate-based corneal storage medium: changes in stromal free sodium.

OBJECTIVES: To evaluate the hydration and the levels of free and total sodium in human corneal stromata preserved for up to 21 days in a dextran and chondroitin sulfate-based corneal storage medium (Optisol-GS, Chiron IntraOptics, Irvine, Calif) and to evaluate the effect of epithelial removal on stromal sodium and hydration parameters. METHODS: Stromal hydration was evaluated thermogravimetrically. A sodium-specific electrode and an atomic absorption spectrophotometer were used to determine the amounts of free and of total stromal sodium, respectively, of preserved human corneas. In 50% of the corneas, the epithelium was removed prior to placement in the storage medium. After 3, 7, 14, or 21 days at 4 degrees C, corneas were removed from the storage medium and sodium measurements were taken. RESULTS: In corneas with an intact epithelium, the stromal hydration as well as the stromal free sodium and total sodium levels were relatively constant up to 21 days of storage in the preservation medium. In the absence of the epithelium, the water and sodium contents of the stroma increased significantly during storage. CONCLUSION: The presence of an intact epithelium is required for maintaining the hydration and sodium levels within the corneal stroma during storage. Removal of the epithelium prior to storage results in increased sodium values and hydration, which may affect postkeratoplasty deturgescence.

Body Water↗
PubMed1998

Human sclera: thickness and surface area.

PURPOSE: To assess the mean thickness and surface area of human sclera. METHODS: Fifty-five formalin-fixed eye bank eyes were hemisected from anterior to posterior. Cross-sectional slides were taken to include a millimeter scale ruler in each photograph. Slide photographs were projected and the scleral silhouette sketched. Mean scleral thickness measurements with standard deviation were obtained. Twenty-five human eye bank eyes were used to determine total scleral surface area by either a computerized tracing method (17 globes) or volumetric calculations (eight globes) using fluid displacement. RESULTS: Mean scleral thickness +/- SD was 0.53 +/- 0.14 mm at the corneoscleral limbus, significantly decreasing to 0.39 +/- 0.17 mm near the equator, and increasing to 0.9 to 1.0 mm near the optic nerve. The mean total scleral surface area by surface area computerized tracings was 16.3 +/- 1.8 cm2 and, by the volume displacement method, was 17.0 +/- 1.5 cm2. CONCLUSIONS: Scleral thickness and surface area measurements from cadaver eyes are important for ophthalmic surgeons and have implications for transscleral diffusion.

Body Surface Area↗
PubMed1998

Effects of laser in situ keratomileusis (LASIK) on the corneal endothelium.

PURPOSE: To assess the effects of laser in situ keratomileusis (LASIK) on the corneal endothelium. METHODS: In a prospective study, the corneal endothelium of 98 eyes of 65 consecutive patients (mean age, 41 years; range, 22 to 66 years) was photographed before, 2 weeks after, and 12 weeks after LASIK for the correction of 2.75 to 14.5 diopters of myopia. Theoretical ablation depths were 200 to 330 microm below the corneal surface. Cell density, coefficient of variation, and percent of hexagonal cells were determined using 150 to 200 cells from each image. Eighty-eight eyes (91%) of 59 patients had a history of contact lens wear. RESULTS: The mean+/-SD preoperative endothelial cell density was 2,549+/-365 cells per mm2, and the mean coefficient of variation was 0.35+/-0.06. There was no statistically significant change in the mean endothelial cell density or mean coefficient of variation of cell size at the 2-week (2,561+/-360 cells per mm2 and 0.35+/-0.06) or 12-week (2,541+/-364 cells per mm2 and 0.35+/-0.05) postoperative examinations. The percent of hexagonal cells was not significantly changed 2 weeks postoperatively; however, 12 weeks postoperatively (P=.0413, two-tailed t test), the percent of hexagonal cells was decreased by 1%. CONCLUSIONS: Corneal endothelial cell density and morphology were unchanged 2 and 12 weeks after LASIK for the correction of up to 14.5 diopters of myopia. In this LASIK study, the correction of up to 14.5 diopters of myopia appears to cause no clinically significant effect on corneal endothelial cell density or morphology.

Adult↗