PubMed HealthSearch

Biomedical subjects

L Cheeks

Publications and source records attributed to L Cheeks.

At least 19 recordsLinked to original sources

Drug interaction with intraocular lenses of different materials.

The uptake and washout kinetics of four drugs representing different classes of ophthalmic medications were measured in intraocular lenses of different materials. The materials ranged from hydrogel lenses to poly(methyl methacrylate) (PMMA), Acrysof (acrylic/methacrylic), and two types of silicone lenses (Chiroflex and AMO SI-18NB). Uptake was determined after seven days of immersion in a large volume of Ringer's solution containing drug concentrations that equaled those found in aqueous humor 30 minutes to one hour after topical administration. Washout was determined after placing lenses in 1 ml of 0.9% saline for 24 hours. Only hydrogel lenses could be digested in acid to measure lens uptake directly. The PMMA, Acrysof, and silicone lenses behaved similarly toward gentamicin and dexamethasone--low uptake (less than 3.5 ng/mg lens) and low washout (less than 4.0%). Their uptake of norepinephrine was lower (less than 0.7 ng/mg lens) but the washout varied from 29% (AMO silicone) to 100% (PMMA and Acrysof). The pilocarpine uptake was the lowest of drugs tested (less than 0.03 ng/mg lens) and the washout varied from 1.5% (acrylic) to 100% (PMMA and Chiroflex silicone). Hydrogel lenses took up the most drug in the following order: dexamethasone greater than pilocarpine greater than gentamicin greater than norepinephrine. Washout was high, ranging from 83% to 98%. Despite the greater uptake and washout, the maximum drug uptake would only provide one-tenth of the greatest aqueous humor concentration that occurs after topical drug administration. Intraocular lenses of the materials tested did not interfere with the intraocular drug pharmacokinetics, nor did the data indicate that presoaking intraocular lenses of these materials in drugs would enhance post-surgical intraocular drug concentrations.

Absorption

Tear potassium contributes to maintenance of corneal thickness.

Isolated rabbit corneas were bathed on their endothelial surfaces with normal Krebs bicarbonate Ringer solution, while the epithelial surfaces were bathed in a basic tear solution containing sodium and potassium. When bathed in basic tear solution alone, corneal swelling occurred at an average of 12 microns/h over a 3-hour period. Corneal swelling occurred at a rate of about 21 microns/h when the epithelial solution was switched from normal basic tear solution to an iso-osmotic K(+)-free basic tear solution. Corneal swelling then slowed, and in the final hour of a 3-hour exposure to K(+)-free tear solution, the corneas deswelled at about 10 microns/h. The data indicate that potassium is a necessary solute for the maintenance of normal corneal thickness. The results suggest that a lacrimal dysfunction that would cause a decrease in the potassium content of tears may influence corneal thickness and also suggest that the inclusion of potassium in artificial tears is important.

Animals

Subconjunctival gentamicin induction of extraocular toxic muscle myopathy.

Subconjunctival injection of commercially available gentamicin, delivered in one of several protocols, caused an acute toxic reaction myopathy of the extraocular muscles. The response began as a small focal infiltrate of polymorphonuclear leukocytes, and as the lesion progressed it assumed a mononuclear cell predominance accompanied by muscle fiber degeneration. The injection of individual components of the commercial preparation (gentamicin, methylparaben, ethylenediaminetetraacetic acid (EDTA) and sodium bisulfite), each at the same concentration as in the parent solution, gave no response except for gentamicin alone. Gentamicin caused acute toxic myopathy when injected away from the muscles and when given as an isotonic solution in saline compared to the hypotonic commercial solution. Solutions at acidic pH not containing gentamicin did not initiate myopathy. Several factors that have been inferred as participating in the toxic response to gentamicin have been eliminated. Gentamicin alone is responsible for the induction of the extraocular muscle myopathy.

Animals

Influence of vehicle and anterior chamber protein concentration on cyclosporine penetration through the isolated rabbit cornea.

The transcorneal penetration of cyclosporine A has been determined from each of three vehicles across isolated cornea into simulated aqueous humor containing either 50 mg % protein (0.5 mg/ml; as found in a normal eye) or 5000 mg % protein (50 mg/ml; as found in an inflamed eye). Cyclosporine entered the corneal epithelium and stroma/endothelium as well as passed through the cornea from an alpha cyclodextrin vehicle. Entry into the epithelium and stroma/endothelium occurred from an ointment vehicle with limited detectable anterior chamber penetration using 50 mg % protein solution in the anterior chamber. From corn oil vehicle, cyclosporine penetrated across the cornea with a permeability equal to that of alpha cyclodextrin vehicle. The concentration of cyclosporine in both corn oil and ointment vehicles is 8 times greater than that in alpha cyclodextrin vehicle resulting in a flux from corn oil vehicle about 7 or 8 times greater than that seen after alpha cyclodextrin vehicle. The amounts retained in the cornea, however, were relatively low after corn oil compared to cyclodextrin. The penetration of cyclosporine from either the cyclodextrin vehicle or ointment was at least doubled in the presence of 5000 mg % protein in the simulated aqueous humor relative to that seen in 50 mg % protein. This data indicates that the (presumed) absorption and binding of drug by the excess protein in the simulated aqueous humor may have removed free cyclosporine from the solution and sustained a high concentration gradient of free solute across the cornea.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Role of toxic ingredients in silicone oils in the induction of increased corneal endothelial permeability.

Silicone oils may induce pathological changes in corneas or retinas by unknown mechanisms but the effects are probably related to certain specific components. Low molecular weight compounds have been implicated in the induction of toxic tissue reactions. Several of these components, that occur as contaminants or by-products in crude silicone oils, were tested for their ability to alter corneal endothelial permeability. In vitro inulin/dextran permeability was measured after one week of in vivo exposure to a non-toxic oil to which various low molecular weight components were added. At least 75% of the anterior chamber volume was replaced with oil +/- additives. A long-chain silanol-terminated polydimethylsiloxane (1000 cps) at 2 mg/ml, tetramethyl-ammonium siloxanolate (a catalyst) at 1 mg/ml and a mixture of a series of linear compounds (MM through MD10M) each at 10 mg/ml all caused a large corneal endothelial permeability increase. A mixture of two short-chain silanol-terminated compounds was less damaging, as was a mixture of a cyclic series. Evidently certain compounds can induce toxic effects on the corneal endothelium whereas other compounds are much less toxic. The linear series and the catalyst, that induce corneal endothelial changes, have been shown to occur in silicone oils.

Animals

Ocular toxicity of subconjunctival gentamicin.

The subconjunctival injection of commercial gentamicin, given either as a single dose or as repeated injections, caused a hyperemic conjunctival response. Simultaneously there was a toxic myopathy induced in the extraocular muscles. The overall response, followed with light microscopy, occurred as a focal infiltrate of polymorphonuclear leukocytes with progression over a few days to a mononuclear cell infiltrate that accompanied fiber degeneration. Injections of each ingredient of commercial gentamicin individually showed that only gentamicin caused the muscle response; methylparaben, EDTA, and sodium bisulfite were without effect. The pH of the solution was eliminated as a contributing factor as was osmolarity of the injection. Increasing recognition is being given to post-operative complications caused by the prophylactic subconjunctival injection of gentamicin following cataract, and other intraocular surgery. The present data offer a mechanistic explanation for many of these toxic findings.

Animals

Corneal endothelial toxicity of dapiprazole hydrochloride.

A new adrenergic antagonist designed for topical use to induce pupillary miosis has been tested for direct toxicity on isolated rabbit corneal endothelium. Dapiprazole hydrochloride was perfused across endothelia in the specular microscope at concentrations from 1.25 micrograms/ml to 1000 micrograms/ml. No toxicity was observed, as determined by corneal thickness determinations over a 3 hour perfusion period, until concentrations greater than 125 micrograms/ml were reached. At 250 micrograms/ml a swelling rate of 17.8 microns/hour occurred, and at 500 micrograms/ml the swelling rate was 17.1 microns/hour; with 1000 micrograms/ml inducing a swelling rate of 23.3 microns/hour. It is evident that the drug concentration that reaches the endothelium after topical application has no toxic effect on the cornea, and that the drug should only be used as directed and not used as an anterior chamber perfusate.

Adrenergic alpha-Antagonists

Intraocular gas effects on corneal endothelial permeability.

We examined the effects of intraocular gases on the permeability of the rabbit corneal endothelium to inulin and dextran. Volumes of air (0.16 ml), sulfur hexafluoride (SF6) (0.08 ml), and octafluoropentane (C3F8) (0.04 ml) were infused into the anterior chamber at constant intraocular pressure so that all volumes were equal after expansion. The inulin/dextran permeability was statistically decreased by infusion with Ringer, while air caused an 8.4% increase in dextran permeability but no effect on inulin flux. These small effects were of no biological significance. SF6 caused a 16% and 13% increase in inulin and dextran permeability, respectively, while C3F8 caused an 18% increase in both inulin and dextran permeability. Longevity of gas in the anterior chamber appears important in delineating the deleterious effects. The gases per se do not appear toxic but rather disrupt normal physiologic function through physical process.

Air

Perfluorocarbon liquid effects on corneal endothelial permeability.

We investigated the effects of perfluoro-n-octane liquid on the rabbit corneal endothelial permeability to inulin and dextran. Permeability measurements were made either after 10 minute in vitro exposure of the endothelium to 50 microliters of the test liquid or after one week exposure in vivo following injection of 50 microliters of the test fluid into the anterior chamber. Retention of the perfluorocarbon on the in vitro cornea and in the anterior chamber during the appropriate exposure time was visually verified. The corneal endothelial permeability was unchanged after either short or sub-chronic treatment with perfluoro-n-octane indicating an absence of toxicity for this substance should it reach the cornea either intraoperatively or postoperatively.

Animals

The effects of intraocular gases on rabbit blood-retinal barrier permeability.

The effects of intravitreal expansile gases, sulfur hexafluoride and octafluoropropane, as well as air and needle insertion alone were assessed by iris fluorescein angiography and blood-retinal barrier permeability determination. Iris angiography, at 3 days after injection, indicated no differences between experimental and paired control eyes. Vitreous fluorophotometry on day 1, day 4 and day 7 after gas or sham injection also showed no differences between paired control and experimental eyes regardless of which experimental condition was employed. The results indicate that these gases are non-toxic to the blood-retinal barrier over a 7 day time course.

Animals

Absence of drug effects on rabbit blood-aqueous barrier permeability to non-electrolytes.

The effects of either topical epinephrine, norepinephrine or pilocarpine upon the entry of non-transported radioactive solutes into the anterior or posterior chamber of pigmented rabbit eyes was examined after intravenous solute perfusion. Solutes employed were urea, thiourea, sucrose and inulin. They were infused at a rate that maintained constant plasma levels from 1 minute through 5 hours of intravenous perfusion. Anterior and posterior chamber samples were taken at either 5 minutes or 5 hours after infusion of solutes, but in either case at 1 hour after drug administration. Differences between the 5 minute and 5 hour data showed more solute entry with the passage of time, and differences were found between the rate of solute entry at both times based upon molecular size. However, while occasional statistically significant differences were found between certain drug treatments, no drug effects were noted on solute entry into the treated eye either when compared to the contralateral untreated eye or to a separate untreated control group.

Animals

Marijuana-derived material-induced changes in monkey ciliary processes differ from those in rabbit ciliary processes.

The morphologic changes in ciliary processes and the associated intraocular pressure (IOP) were observed in owl and squirrel monkeys after intravitreal (IVT) and intravenous (IV) injections of water soluble marijuana-derived material (MDM). The response in monkeys differed from that reported in rabbits wherein IV injection induced severe ciliary swelling and a significant decrease in IOP. Only moderate swelling occurs in monkey processes after IV injection of relatively high dose of MDM, and this change, which includes disruption of the basal lamina of the pigment epithelium, is not associated with a change in IOP. Severe swelling occurs in the crests of monkey ciliary processes after IVT injection, which is accompanied by a fall in IOP. The difference in the response in monkey versus rabbit ciliary processes after IV injection of MDM may be due to a more compact stroma in the monkey processes.

Animals

Hydrogen peroxide effects on ionic and non-ionic permeability of the rabbit corneal endothelium.

Perfusion of the isolated rabbit corneal endothelium with 0.3 mM hydrogen peroxide (H2O2) caused an increased passive permeability to bicarbonate relative to control tissues. This was accompanied by a reduction in the active flux that resulted in a reduced net bicarbonate flux. Perfusion with 0.3 mM H2O2 resulted in a marked increase in the active and net flux of sodium beginning at two hours. By four hours the net sodium flux had increased by nine-fold over control values. Perfusion with 0.3 mM H2O2 resulted in a 16% and 30% increase in endothelial permeability to inulin and dextran, respectively. Suppression of catalase activity by in vivo pretreatment with intravenous 3-aminotriazole (3AT) did not result in an increased sensitivity of the corneal endothelium to 0.2 mM H2O2: both bicarbonate and sodium fluxes were normal. Inhibition of glutathione synthesis with intravitreal buthionine sulfoximine (BSO) increased the sensitivity of the corneal endothelium to 0.2 mM H2O2 only in the case of sodium flux, with a 4.8-fold increase in net sodium flux at 3 hours after initiation of perfusion. Bicarbonate fluxes were unaffected after BSO pretreatment. The data show that ionic and non-ionic fluxes are altered by H2O2, that pretreatment with 3AT has a minimal effect on ion fluxes while BSO markedly alters sodium flux without changing bicarbonate fluxes, and that sodium and bicarbonate movement are not locked in a symport.

Amitrole

Effects of thymoxamine on corneal endothelium.

We have investigated the effects of 0.02 and 0.2% thymoxamine hydrochloride on the isolated rabbit corneal endothelium. The corneal swelling rate, measured by specular microscopy, indicated that 0.02% thymoxamine caused a swelling rate equal to controls while a 0.2% concentration caused a significantly increased swelling rate (34.1 vs 10.3 microns/h; P less than 0.05). The data suggests that the maximum recommended intracameral concentration of thymoxamine be 0.02% in order to allow a 10-fold safety factor for the corneal endothelium.

Animals

Interactions of benzalkonium chloride with soft and hard contact lenses.

We measured the uptake and washout of benzalkonium chloride, using radioactive tracer, by representative hard and soft contact lenses. Uptake by soft contact lenses after 7 days of continuous exposure is high (30 to 56 micrograms/mg of lens weight), with a low percentage of washout in 24 hours (between 0.2% and 1.5% of total uptake). High-water content lenses absorb greater quantities of benzalkonium than do low-water content lenses. Hard lenses take up a much smaller quantity of benzalkonium but release between 30% and 60% of total uptake during washout for 24 hours. Fluorosilicone-acrylate polymer lenses adsorb and release the most preservative, while polymethylmethacrylate lenses (Paragon Optical Inc, Mesa, Ariz) adsorb and release the least. The released benzalkonium from either soft or hard lenses is of a sufficient concentration to be at or above the upper limits of safety.

Benzalkonium Compounds

Corneal endothelial permeability after anterior chamber silicone oil.

One of six silicone oils, differing in both viscosity and manufacture, was infused into the anterior chambers of rabbit eyes. Polydimethylsiloxane oil, 5000 cps, caused an increased corneal endothelial permeability to inulin and dextran at 24, 96, and 168 hours after placement into the eye. Intraocular pressures were slightly elevated in the experimental eyes, compared with contralateral controls, at 24 and 144 hours after infusion. The effects of five other oils on corneal endothelial permeability were examined 168 hours after infusion. All oils increased permeability and caused thinning of endothelial cells, together with the appearance of a retrocorneal membrane, except Dow Corning Medical Fluid 360. The results indicated that contact of most silicone oils with corneal endothelium rapidly induces physiologic and morphologic changes.

Animals

Relationship between plasma and tear fluoride levels in rabbit and man.

Tear fluoride concentrations were determined in rabbits and man. Tear fluoride levels in reflex tears were higher in rabbits (2-10 mumol/l) than in man (1.4-4 mumol/l), while plasma levels were quite similar in both species (1.5-4 mumol/l). Chronic fluoride ingestion in rabbits over 29 days of 1, 5, 10, 25 or 50 (2.65 mmol/l) ppm fluoride in drinking water caused a dose-related increase in plasma, but not tear, levels of fluoride. The plasma:tear ratio went from 0.5 at baseline (1 ppm) to 1.8 after drinking water that contained 50 ppm F. Acute fluoride ingestion in man led to an increase in both plasma and tear fluoride levels that changed such that the plasma:tear ratio remained constant despite a 2-fold increase in plasma fluoride.

Animals

Effects of mifepristone on rabbit intraocular pressure in the presence and absence of dexamethasone.

Topical dexamethasone was used to elevate rabbit intraocular pressure in order to study the interaction with a steroid antagonist, mifepristone. Dexamethasone did not cause a consistently significant increase in intraocular pressure. Animals treated with mifepristone followed by dexamethasone showed no apparent increase in intraocular pressure after dexamethasone, indeed mifepristone caused a lower intraocular pressure than seen in other groups whether in the presence or absence of dexamethasone. Reductions of intraocular pressure when mifepristone was given after 14 days of dexamethasone administration were not found. No conclusion can be reached regarding any dexamethasone antagonism by mifepristone, except that intraocular pressure tended to be lower even in the presence of dexamethasone.

Administration, Topical