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Biomedical subjects

H F Edelhauser

Publications and source records attributed to H F Edelhauser.

At least 109 records · Page 6Linked to original sources

The corneal toxicity of presurgical skin antiseptics.

In a study of the corneal toxicity of some commonly used presurgical skin antiseptics, we used biomicroscopy, corneal pachymetry, healing studies, and electron microscopy to compare tincture of iodine (2% iodine, 2.35% sodium iodine, and 46% ethanol), Hibiclens (4% chlorhexidine and 4% isopropyl alcohol with detergent), pHisoHex (3% hexachlorophene and detergent), Lavacol (70% ethanol), 7.5% povidone iodine scrub (with a detergent), and 10% povidone iodine solution (without a detergent) in rabbits. Five minutes after application, moderate corneal epithelial edema was noted in all groups except the saline control group. After three hours there was marked corneal de-epithelialization, conjunctival chemosis, and anterior stromal edema in all groups except those treated with 10% povidone iodine solution and 0.9% sodium chloride. After one week all corneas had returned to normal. Accidental instillation of 7.5% povidone iodine scrub into the tear film of a 33-year-old man resulted in almost immediate chemical chemosis despite prompt irrigation, demonstrating the corneal toxicity of this substance. These results indicated that a 10% povidone iodine solution without detergent causes minimal corneal toxicity whereas the other presurgical skin antiseptics tested are toxic to the cornea.

Adult↗

Classification of corneal endothelial disorders based on neural crest origin.

The corneal endothelium is derived from the neural crest. A general classification of disorders of development of the neural crest has been previously presented (Johnston). Disorders of the corneal endothelium may be considered according to a modification of this scheme to reflect its true embryologic origin. In this classification, corneal endothelial disorders are categorized as abnormalities of neural crest cell formation (cyclopia), migration (Peters' anomaly), proliferation (iridocorneal endothelial syndrome), final differentiation (Fuchs' dystrophy), and acquired abnormalities (metaplasia, abiatrophy, and proliferation).

Adult↗

The effects of ouabain on endothelial function in human and rabbit corneas.

These experiments were undertaken to study the effects of ouabain on endothelial function in isolated perfused human and rabbit corneas. Both human and rabbit corneas swell at rates which are dose-dependent when perfused with ouabain (10(-8) to 10(-5) M). The human tissue, however, requires tenfold higher concentrations to achieve swelling rates comparable to rabbit. Dose-dependent ultrastructural changes are seen in ouabain-perfused endothelia progressing from moderate endothelial edema (7.5 X 10(-7) M) to marked edema with altered subcellular organelles and vacuolization (10(-5) M). Ouabain-perfused human corneas show marked endothelial edema even at the lowest concentrations of ouabain tested. Apical junctions remain intact, however, in both human and rabbit endothelia at all concentrations. These results suggest that endothelial Na/K ATPase is essential to pump function in both human and rabbit corneas.

Aged↗

Quantitation of Na/K ATPase pump sites in the rabbit corneal endothelium.

In these experiments, the binding of 3H . ouabain, a specific inhibitor of Na/K ATPase, was used to quantitate the density of Na/K ATPase pump sites in the rabbit corneal endothelium. The uptake of ouabain by the corneal endothelium shows two components: one that saturates at a ouabain concentration near 2 X 10(-7) M (specific binding), and one component that increases linearly with increasing glycoside concentration (nonspecific uptake). The nonspecific uptake can be accounted for by that ouabain equilibrating with the extracellular space, which, estimated by inulin space, amounts to 13.0 nl/mm2 of endothelium. The saturable component of endothelial ouabain uptake is displaced by K+ ions, which is consistent with this fraction being bound to Na/K ATPase. Maximal endothelial ouabain binding was measured as 20.7 fmoles/mm2 of endothelium, which corresponds to 3.0 X 10(6) pump sites per cell. The density of Na/K ATPase pump sites in the rabbit corneal endothelium is comparable to densities reported for several transporting epithelia. These data are consistent with the known function of the endothelium in corneal deturgescense and corroborate the importance of Na/K ATPase in endothelial fluid transport.

Animals↗

Comparison of intraocular irrigating solutions used for pars plana vitrectomy and prevention of endothelial cell loss.

We performed a prospective study of corneal endothelial cell loss following pars plana vitrectomy. Two different intraocular irrigating solutions were used, and the anterior capsule of the lens was removed when performing lensectomy. The central corneal endothelium was photographed with a specular microscope before and at three months after vitrectomy. Endothelial cell loss was calculated using a computer-assisted digitizer. In the 16 aphakic eyes, lactated Ringer's solution caused a significantly greater cell loss (31.1%) with resultant corneal edema when compared to BSS Plus (6.9%). All of the 17 phakic eyes showed minimal cell loss (1.0%) as well as corneal changes regardless of the kind of irrigating solution used. The results suggest that the absence of the lens is a salient factor in corneal endothelial damage during vitrectomy, and that the composition of the intraocular solution used is closely related to this endothelial damage.

Acetates↗

Pharmacokinetics of topical ocular phenylephrine HCl.

The rates of corneal penetration and efflux of phenylephrine (PE) and its metabolites were found to be limited by the epithelium. The rate constant for corneal penetration as measured in a lucite block perfusion system was 1.06 X 10(-3) hr-1 when the epithelium was present and 1.25 X 10(-2) hr-1 when the epithelium was denuded. Epithelial removal reduced the half-time (t1/2) for corneal efflux of PE from 24 min to 6 min. Ocular absorption of topically applied 0.1% PE (three 30-microliters instillations at five-minute intervals) was increased when the corneal epithelium was removed prior to application. Corneal concentrations of PE increased threefold, aqueous humor concentrations increased ten to 13-fold and iris/ciliary body concentrations increased sixfold upon epithelial removal. HPLC analysis suggested that the corneal epithelium was responsible for the metabolic degradation of PE, which occurred following topical instillation of PE.

Absorption↗

The transcorneal permeability of sulfonamide carbonic anhydrase inhibitors and their effect on aqueous humor secretion.

Eleven sulfonamide carbonic anhydrase inhibitors of varied chemical and physical types were studied with respect to transcorneal permeability and reduction of intraocular flow and pressure. Using the isolated rabbit cornea, a constant drug concentration on the epithelial side and 6 ml solution in the endothelial chamber, first order rate constants (kin) ranged from 0 . 1-40 X 10(-3)/hr, roughly proportional to their lipid solubility. Drugs on the high side of this range were generally water insoluble and had pKa's too high to yield sodium salts at useful pH; therefore, the actual amount of drug delivered was small. We sought compounds which combined low pKa, good lipid solubility, and high activity against the enzyme. Trifluormethazolamide (TFM) has a pKa of 6 . 6, ether partition coefficient of 6, and a K1 of 2 X 10(-8)M. kin is 3 X 10(-3)/hr. TFM and five other compounds were also studied in vivo for their ability to penetrate the eye into the anterior and posterior chambers. These rate constants were roughly proportional to those measured in vitro; however, significant differences in accession to the two chambers were observed, as a function of varying physico-chemical properties of the drugs. A 3% solution of TFM (100 mM) applied to the rabbit eye for 25 min generated 0 . 7 mM in the anterior chamber and 0 . 07 mM in the posterior. Tissue distribution of TFM (and its metabolite) showed a relatively high concentration in the ciliary body 6 hr after dose. Intraocular pressure was reduced by 4 mmHg. With 10 min exposure this concentration of TFM reduced pressure by about 1 . 7 mmHg. Although the use of this drug is limited by its chemical instability and the length of exposure needed, the principle of treating glaucoma by the topical use of carbonic anhydrase inhibitors appears feasible.

Animals↗

The effects of sodium hyaluronate, chondroitin sulfate, and methylcellulose on the corneal endothelium and intraocular pressure.

Sodium hyaluronate (Healon), chondroitin sulfate, and methylcellulose have been used to protect the corneal endothelium from intraocular lens trauma. A study of the efficacy and toxicity of these compounds showed that 1% sodium hyaluronate, 0.4% methylcellulose, and 20% chondroitin sulfate were nontoxic to the corneal endothelium, but that 20% chondroitin sulfate caused a marked decrease in corneal thickness because of its hypertonicity. Anterior chamber injection of these viscous substances resulted in an increase in intraocular pressure. Within one to four hours the maximum intraocular pressure with 1% sodium hyaluronate was 67 +/- 4.1 mm Hg and that with 20% chondroitin sulfate was 55 +/- 3.5 mm Hg. The intraocular pressure did not increase to these high levels with 10% chondroitin sulfate or 0.4% methylcellulose or when the test substances were washed out of the anterior chamber. The corneal endothelium was protected from injury with 1% sodium hyaluronate and 20% chondroitin sulfate, but 10% chondroitin sulfate and 0.4% methylcellulose provided only minimal protection.

Animals↗

Healing of experimental corneal wounds treated with topically applied retinoids.

We treated experimental corneal epithelial wounds in rabbits with topical retinoids. Treatment with 0.1% all-trans-retinoic acid three times per day resulted in a 21% increase in the healing rate compared to the control eyes. Treatment five times a day resulted in a 35% increase in healing rate. Treatment with topical retinoic acid also promoted corneal deturgescence. Retinyl palmitate, retinyl acetate, retinol, and 13-cis-retinoic acid had no effect on corneal wound healing. These data suggested that topically applied all-trans-retinoic acid may be effective in promoting corneal healing after surgery and in the treatment of persistent and recurring corneal epithelial defects.

Administration, Topical↗

Retinoid permeability and uptake in corneas of normal and vitamin A-deficient rabbits.

In vitro perfusion of corneas of normal and vitamin A-deficient rabbits provided a model in which to study the pharmacokinetics of corneal permeability and uptake of retinoic acid and retinol. The permeability coefficients of retinoic acid and retinol were 1.49 x 10(-5) and 0.61 x 10(-5) cm/s, respectively. Removal of the corneal epithelium did not affect the permeability of these lipid-soluble retinoids; however, diffusion through xerophthalmic, vitamin A-deficient corneas was significantly reduced. The corneal uptake of retinoic acid and retinol was reduced by 50% on removal of the epithelium, was nonspecific, and was not affected by xerophthalmia. High-performance liquid chromatography indicated that these retinoids were not metabolized during diffusion through the cornea. These results show that topical application of retinoids is a rational approach to the treatment of such corneal diseases as xerophthalmia and epithelial defects.

Animals↗

The effect of intraocular irrigating solutions on lens clarity in normal and diabetic rabbits.

We conducted a series of experiments on normal and diabetic rabbits to evaluate the effect of intraocular irrigating solutions on the lens. Lenticular clarity was studied in vivo in eyes undergoing vitreous cavity perfusions with various irrigating solutions. The clarity of isolated lenses incubated in these same solutions was also evaluated. In order to quantitate the cataractous changes observed, we measured the uptake of inulin (tagged with radioactive carbon) by isolated lenses. We found that balanced salt solution (BSS) and BSS Plus maintain excellent lens clarity in normal rabbits; that diabetic lenses are more likely to develop opacification than normal lenses, becoming cataractous when exposed to BSS Plus; and that adding supplemental glucose to BSS Plus allows this solution to maintain excellent lens clarity in diabetic rabbits.

Animals↗

Corneal edema and the intraocular use of epinephrine.

Commercially prepared dilutions (1:10,000) of epinephrine can cause marked increases in corneal thickness and loss of corneal endothelial cells when injected into the anterior chamber of the eye. Endothelial toxicity is related to the buffer capacity of the epinephrine solution, which is in turn controlled by the concentration of the antioxidant (sodium bisulfite) as well as by the vehicle formulation and a low pH value.

Animals↗

A comparison of healing of corneal epithelial wounds stained with fluorescein or Richardson's stain.

The effects of fluorescein and Richardson's stain on corneal epithelial wound healing were compared in eyes of rabbits whose corneas had the epithelium removed by scraping or by n-heptanol. One eye of each rabbit was stained with fluorescein and the other eye was stained with Richardson's stain at intervals throughout the healing process, and the wounds were photographed for planimetry and determination of re-epithelialization rate. Corneal thickness was also measured throughout the re-epithelialization. These studies showed that Richardson's stain, as compared with fluorescein, decreases re-epithelialization rate, delays wound closure, and slows the return of the edematous cornea to normal thickness. Therefore fluorescein rather than Richardson's stain should be used to stain epithelial defects in corneal wound healing studies and in the evaluation of the corneal toxicity of chemical agents.

Animals↗

The corneal endothelium. Normal and pathologic structure and function.

A summary of normal and abnormal endothelial structure and function is presented. Endothelium originates from neural crest and it elaborates a banded basement membrane in utero. It is involved in mesenchymal dysgenesis of the anterior segment, like the central defect of Peters' anomaly. Cytoplasmic organelles include mitochondria that provide energy for the metabolic pump, rough endoplasmic reticulum that participate in secretion of extracellular matrix, and a terminal web that may participate in cell migration. The endothelium's main function is to control corneal hydration and nutrition with a leaky barrier formed by the apical gap and macula occludens junctions that keep some water out of the stroma but allow nutrients to pass, and with an ATPase-dependent metabolic pump that is located in the lateral plasma membranes. Endothelial wound healing involves flattening and enlargement of cells to maintain an intact monolayer as well as production of abnormal collagenous material posterior to Descemet's membrane. HLA antigens located in the plasma membrane may participate in corneal endothelial graft rejection. Clinical assessment of the endothelium involves three modalities: specular microscopy to study endothelial morphology, fluorophotometry to measure barrier function, and pachymetry to measure corneal thickness.

Adolescent↗

Osmotic tolerance of rabbit and human corneal endothelium.

Rabbit and human corneas were mounted in a specular microscope and perfused with a balanced salt solution of varying osmolality (200 to 500 mOsm). Measurements of corneal thickness were made throughout the perfusion period, and at selected times the corneas were fixed and prepared for scanning and transmission electron microscopy. A hypo-osmotic perfusion medium caused an increase in corneal thickness; by comparison, a hyperosmotic perfusion medium decreased corneal thickness in both rabbit and human corneas. Despite the marked changes in corneal thickness and the water movement that occurred across the endothelium, the cellular ultrastructure remained intact. In reversal studies (return to 300-mOsm perfusion medium), corneal thickness returned to control values with no marked changes in endothelial cell structure. These data indicate that the corneal endotheium can tolerate a wide range of solution osmolalities (200 to 400 mOsm) without marked endotheial cell breakdown if the essential ions are present.

Animals↗