Tissue plasminogen activator and the corneal endothelium.
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Endothelium, Corneal↗
Biomedical subjects
H F Edelhauser
Publications and source records attributed to H F Edelhauser.
Drug binding of ophthalmic viscoelastic agents.
When viscoelastic agents that contain hyaluronate sodium are used during anterior segment surgical procedures, it is common for some of the material to remain intraocularly after the surgery is completed. A variety of drugs, used intracamerally or topically following surgery, are also present. These drugs may be bound to the polyanionic hyaluronate molecule. This occurrence may cause drug alterations in therapeutic effectiveness, pharmacokinetics, and toxicity. To investigate the possibility for drug-viscoelastic agent adsorption, in vitro drug-binding studies were performed on three commercial viscoelastic agents; undiluted aliquots of Amvisc, Healon, or Viscoat were mixed with radiolabeled D-threo-chloramphenicol, dexamethasone, L-epinephrine, or pilocarpine hydrochloride, placed in dialysis membranes, and dialyzed for 24 hours against an isotonic phosphate buffer. The calculated drug binding by a viscoelastic agent ranged from 0% to 1.5%. These extremely low values for in vitro drug uptake by viscoelastic agents made it unlikely that any significant drug-viscoelastic agent interaction would occur in the postoperative eye.
Chondroitin↗
In vitro corneal endothelial permeability in rabbit and human: the effects of age, cataract surgery and diabetes.
Endothelial permeability was examined in rabbit and human corneas using an in vitro perfusion system with 5(6)-carboxyfluorescein as the permeability tracer. Following endothelial removal, the permeability of de-epithelialized rabbit corneas increased from 3.19 x 10(-4) cm min-1 to 31.21 x 10(-4) cm min-1, and de-epithelialized human donor corneal permeability values increased from 2.26 to 12.85. In human corneas, no correlation was seen between endothelial permeability and donor age, moist chamber storage time, endothelial cell density, coefficient of variation of cell area, or percent hexagonal cells. A positive correlation was found between permeability and time between donor death and enucleation. Donor eyes from three separate populations, having undergone cataract surgery prior to death (aphakic, posterior and anterior chamber implants), all showed a significant increase in permeability. Neither Type I nor Type II diabetes had an effect on the endothelial permeability of human donor corneas.
Aging↗
Drug uptake and release by a hydrogel intraocular lens and the human crystalline lens.
Implantation of a hydrogel (IOGEL) intraocular lens in humans has been reported. The polyhydroxyethyl methacrylate (poly HEMA) matrix of this hydrogel is permeable to water soluble drugs and may adsorb agents used intracamerally during cataract extraction or topically during the postoperative period. This study compared the in vitro uptake and release of chloramphenicol, dexamethasone, epinephrine, pilocarpine, and bovine serum albumin by polymethylmethacrylate and hydrogel intraocular lenses with that of the intact crystalline lens of humans and rabbits. An in vivo study compared the uptake and release of chloramphenicol and dexamethasone by hydrogel lenses implanted in the anterior chamber of rabbit eyes with that of the rabbit's crystalline lens. The in vitro uptake and washout of epinephrine and pilocarpine by the hydrogel lens was comparable to the human lens. Uptake of chloramphenicol and dexamethasone by the hydrogel lens exceeded that of the human lens and, following a two-hour washout period, the dexamethasone content of the hydrogel lens remained significantly greater than the human lens. The uptake and washout of bovine serum albumin by the hydrogel lens was half that of the human lens. In vivo, the hydrogel lens efficiently eluted both chloramphenicol and dexamethasone. These studies show that a hydrogel lens will not act as a significant depot for drugs in the eye.
Animals↗
Toxicity of surgical solutions.
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Anti-Infective Agents, Local↗
Morphometric analysis of the corneal endothelium. Specular microscopy vs. alizarin red staining.
Computer-assisted analysis of endothelial morphology provides useful indices of cell shape and size which appear to correlate to the monolayer's functional status. In this study morphometric data obtained by wide-field specular microscopy of in situ corneal endothelia are compared to data obtained by alizarin red S staining of excised corneas. Both human donor corneas and rabbit corneas were studied. The results of the study indicate that considerable (14%) cell shrinkage occurs in rabbit endothelia following staining. Associated with this cell shrinkage is a normalization of cell area which is manifest as a significant (P less than 0.001) decrease in the coefficient of variation of cell area. The percentage of hexagonal cells, however, remains unchanged. These changes were not mitigated by lowering the osmolality of the saline rinse following staining or by minimizing evaporation by placing a drop of silicone oil on the stained button. In human tissue no significant differences in cell area or cell shape were noted in comparing morphometric data obtained by staining to that obtained from specular microscopy. Useful morphometric data can be obtained by alizarin staining. This technique combined with cell morphometric analysis could provide valuable data in corneas whose lack of clarity limits or precludes specular microscopy. Caution, however, must be exercised in comparing morphometric data by this method to those obtained in situ for rabbit tissue.
Animals↗
Intracameral thrombin and the corneal endothelium.
We perfused the endothelia of isolated human corneas mounted in the specular microscope with BSS Plus containing 1,000-U/ml or 100-U/ml dilutions of two commercially available topical thrombin preparations. Corneas perfused with thrombin at 1,000 U/ml showed intracellular and intercellular vacuole formation and altered junctional complexes. As listed on the package inserts, the thrombin preparations contained preservatives and other additives that present a significant osmotic load in 1,000-U/ml preparations. Corneas perfused with 100-U/ml thrombin solutions showed a significant attenuation in their deswelling rate but no ultrastructural alterations. One available thrombin preparation when diluted to 100 U/ml had a glycine concentration associated with previous retinal electroretinography changes. Polyacrylamide gel electrophoresis of one manufacturer's thrombin solution showed multiple high and low molecular weight constituents. Analysis of particulate contamination showed one 100-U/ml thrombin preparation to have a large quantity of particulates. Although thrombin may be useful when applied topically as an aid in surgical hemostasis, its use intraocularly presents substantial concern regarding the preparation's purity, additives, contaminants, and adverse effects on ocular tissues.
Aged↗
Permeability of human cornea and sclera to sulfonamide carbonic anhydrase inhibitors.
Corneal penetration of sulfonamide carbonic anhydrase inhibitors for topical treatment of glaucoma has been tested in human eye bank and rabbit tissue. Paired corneas, with the epithelia intact or removed, and excised sclera were perfused in vitro. Corneal permeability (Kp) to methazolamide and ethoxzolamide was similar in both species, but for benzolamide and bromacetazolamide the Kp was greater in humans. Human corneas without epithelium had Kp the same as scleral Kp. Topical methazolamide (6 mmol/L) was studied in vivo in rabbits and in ten humans before cataract surgery. The mean (+/- SE) concentration in the rabbit aqueous was 3.2 +/- 1.4 mumol/L at eight minutes and 1.2 +/- 0.16 mumol/L at one hour. In humans, less than 0.2 mumol/L was detected at eight minutes; at one hour none was detected in three cases, and 0.4 +/- 0.08 mumol/L was detected in four cases. Lower permeability in humans than rabbits may result from a fourfold greater blinking rate, a twofold greater tear turnover, and a twofold lower corneal/conjunctival area.
Aged↗
Comparison of conjunctival and corneal surface areas in rabbit and human.
This comparative study shows the surface area ratio of conjunctiva to cornea to be two times larger in humans than in rabbits. This large heretofore unrecognized interspecies difference may affect the applicability of drug pharmacokinetic data obtained using rabbit models and should be taken into consideration in topical drug development and future comparative drug penetration studies between rabbit and man.
Animals↗
Corneal endothelial morphology in the rat. Effects of aging, diabetes, and topical aldose reductase inhibitor treatment.
Increases in corneal endothelial cell polymegathism and pleomorphism are characteristic of diabetic human and dog corneas. This study investigated the rat as a model for age- and diabetes-related changes in endothelial cell morphology. As in most mammals, aging of the normal rat results in a progressive decrease in cell density as well as reduced numbers of hexagonal endothelial cells and increased coefficient of variation of cell size after age 34 weeks. Streptozotocin-induced diabetes produced an early progressive increase in the coefficient of variation of cell size and decrease in percentage of hexagonal cells so that diabetic rats were significantly different from age-matched normal rats by 24 weeks of age. Topical treatment with the aldose reductase inhibitor, AL 1576, begun immediately after diabetes induction, prevents endothelial cell changes and cataract formation. Topical aldose reductase inhibition also reverses endothelial cell changes when treatment is begun 8 weeks after streptozotocin injection. These results indicate that the rat is a good model for studying diabetes-induced corneal endothelial changes and that topical aldose reductase inhibitors may be effective in preventing or reversing diabetic corneal endothelial cell changes.
Aging↗
Ophthalmic irrigants: a current review and update.
The search for an ideal intraocular irrigating solution is of paramount importance to te ophthalmic surgeon. An intraocular irrigating solution, as well as surgical technique, can have deleterious effects on ocular tissues. Since an intraocular irrigating solution comes in contact with the cornea, lens, trabecular meshwork, uvea, vitreous, and retina, and ideal irrigant would be ome that ensures biological function for all of these tissues. In a practical sense, the best irrigant is one that causes the least possible damage to the structural integrity and function of the intraocular environment. This paper summarizes the development, uses, and efficacy of intraocular irrigating solutions as currently used during intraocular surgery.
Animals↗
Specular microscopy of vertebrate corneal endothelium: a comparative study.
Central corneal endothelia in a variety of lower- and higher vertebrate animals were photographed with a widefield specular microscope and analysed with either fixed-frame or computer-assisted morphometric analysis. The endothelium of the dogfish shark, an elasmobranch, contained 2300 cells mm-2 and demonstrated a very delicate irregular 'reversal pattern'. The goldfish, a teleost, had 432 cells mm-2 and displayed a jigsaw-puzzle-like pattern. The bullfrog, an amphibian, and the gecko, a reptile, had 550- and 481 cells mm-2, respectively, and a relatively uniform polygonal endothelial pattern similar to that observed in mammals. The goose, a bird, had a cell density of 2410 cells mm-2 with a uniform hexagonal pattern (79%) which was similar to mammalian (rat, 58-76%; rabbit, 71%; dog, 78%; human, 61-75%) hexagonal patterns. The findings on the endothelial appearance in these vertebrate animals suggest that a correlation exists between endothelial morphology, vertebrate phylogeny and their respective functional and structural capacity.
Animals↗
Treatment of corneal xerophthalmia in rabbits with micromolar doses of topical retinoic acid.
Several reports have appeared on the efficacy of topically applied 0.01% or 0.1% all-trans retinoic acid (0.04-0.4 millimolar) for treatment of xerophthalmia, conjunctival squamous metaplasia, and corneal epithelial erosions in humans and animals. An observation common to many of these studies is the occurrence of an adverse reaction to retinoic acid in the form of lid margin hyperemia and blepharoconjunctivitis. Since retinoic acid is biologically active at micromolar to nanomolar concentrations, it may be possible to reduce side effects while maintaining therapeutic effectiveness by reducing the retinoic acid concentration in ophthalmic formulations. In the present study, topical 0.005% retinoic acid in petrolatum ointment reversed corneal keratinization in xerophthalmic, vitamin A-deficient rabbits in 3-4 days while 0.0005% (2 micromolar) retinoic acid ointment was effective in 4-6 days. Further clinical trials of topical retinoic acid for treatment of ocular surface disease should be conducted using micromolar concentrations of retinoic acid which are expected to maintain a therapeutic effect while reducing adverse reactions.
Administration, Topical↗
Effect of inflammation on the corneal endothelial pump and barrier.
Corneal thickness is a reflection of endothelial barrier and pump functions. The corneal edema that occurs during intraocular inflammation is a consequence of the breakdown of one or both of these parameters. Results of this study demonstrate that, during intraocular inflammation induced by an intravitreal injection of bovine serum albumin (BSA), the permeability of rabbit corneal endothelia to inulin was increased. By comparison, treatment with oral aspirin and/or subconjunctival triamcinolone acetonide prevented the endothelial barrier breakdown induced by the BSA. Concomitant with the loss of the barrier function, endothelial ouabain binding decreased in the BSA injected eye, indicating a reduction in endothelial Na/K ATPase pump site density. A subconjunctival injection of triamcinolone prevented this decrease in pump sites. The increase in endothelial permeability and the decrease in pump site density correlated with an increase in corneal thickness. It can be concluded that the intraocular inflammation induced by BSA effects corneal edema by both an increase in endothelial permeability and a decrease in Na/K ATPase pump site density. Subconjunctival triamcinolone is effective in preventing this response.
Animals↗
Specular microscopic evaluation of donor corneal endothelium.
We performed wide-field specular microscopy and pachymetry on 92 donor corneas to evaluate the changes occurring in the endothelium during moist chamber storage of up to 48 hours. Endothelial changes were quantitated with computer-assisted morphometry. The donor corneas were divided into two groups: younger (mean age, 34 years) and older (mean age, 72 years). No significant differences in endothelial cell density, coefficient of variation in cell area (polymegethism), percentage of hexagonal cells (pleomorphism), or central corneal thickness were noted between younger and older donors when storage intervals were similar. Within each group, while endothelial cell density remained constant, a marked increase in polymegethism and pleomorphism developed when storage was prolonged beyond 12 hours. Corneal thickness also increased, but there was no correlation between thickness and the extent of the endothelial changes. These results suggest that specular microscopy is a more reliable method of screening donor tissue than donor age or corneal thickness.
Adolescent↗
Response of the corneal endothelium to cataract surgery.
Regional changes in endothelial cell density, morphology, and corneal thickness were serially examined with a specular microscope after intracapsular cataract extraction (four eyes), extracapsular cataract extraction (five eyes), and extracapsular cataract extraction with posterior chamber lens implantation (13 eyes). Regardless of the type of cataract surgery, cell loss and morphologic changes (decreased percentage of hexagonal cells, increased cellular elongation, and increased coefficient of variation) were greatest and occurred within one week in the superior cornea. Similar changes occurred after one month centrally but were minimal inferiorly. Endothelial cell density stabilized, and the morphologic changes resolved within three months in all regions of the cornea. Corneal swelling resolved within one month. Differences between the procedures were noted only in the superior portion of endothelium, where cell loss and morphologic changes were greatest following intracapsular cataract extraction. Also, endothelial wound healing was complete and stable three months after cataract surgery, with or without posterior chamber lens implantation.
Adult↗
A comparison of the efficacy and toxicity of and intraocular pressure response to viscous solutions in the anterior chamber.
An intraocular-lens abrasion test, vital dye staining, and scanning electron microscopy were used for an in vitro comparison of endothelial protection offered by four viscous solutions of 1% sodium hyaluronate (Healon), 3% sodium hyaluronate (AmVisc), 4% chondroitin sulfate (Viscoat), and 2% methylcellulose. Wide-field specular microscopy with analysis of endothelial cell density and morphologic evaluation, pachymetry, and intraocular pressure measurements were also used to study the toxicity of the viscous solutions in an in vivo cat model with and without anterior chamber washout. All four solutions provided complete endothelial protection from mechanical trauma. Endothelial cell density and morphologic nature were unaffected during the in vivo toxicity study. A mild increase in intraocular inflammation occurred at one and two days after intraocular injection with all four viscous solutions. Intraocular pressure elevations peaked within four hours after instillation of the viscous solutions and were significantly reduced by anterior chamber washout.
Animals↗
Comparison of intraocular acetylcholine and carbachol.
Commercially available 1% acetylcholine chloride and 0.01% carbachol chloride, which are commonly used as miotics in intraocular surgery, have recently been reformulated. Comparative studies of these agents show similar miotic activity. However, in vitro perfusion of human corneas demonstrated that 1% acetylcholine chloride causes marked changes in endothelial function and ultrastructure as compared to carbachol or BSS Plus. This study showed that 0.01% carbachol chloride was less toxic to the corneal endothelium than 1% acetylcholine chloride and suggests that 1% acetylcholine should not be used in corneas with compromised endothelium as in primary corneal endotheliopathies.
Acetylcholine↗