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Biomedical subjects

R O Schultz

Publications and source records attributed to R O Schultz.

At least 19 recordsLinked to original sources

Overview of the corneal toxicity of surgical solutions and drugs: and clinical concepts in corneal edema.

Surgical solutions and drugs are important in ocular surgery. These include irrigating solutions, viscoelastic substances, mydriatics and miotics, and a growing number of other agents designed to enhance intraocular surgery and its outcome. Potential for damage to the corneal endothelium and other tissues is related to the chemical composition, pH, and osmolality of the irrigating solutions that bathe tissues. Quality balanced salt solutions (BSS) are usually safe for use as an intraocular solution in patients with normal corneal endothelium. If prolonged irrigation times are expected, or the patient already has decompensated endothelium, i.e., primary or secondary endotheliopathy, the use of a "complete" BSS solution is indicated to minimize damage. Intraocular sulfite-containing epinephrine may cause severe corneal edema and should be avoided, or if used, be well diluted. Sulfite-free epinephrine solution is now available and does not cause the endothelial toxicity that one may see with sulfite-containing epinephrine solutions. Current formulations of acetylcholine and carbachol used as miotics in surgery have been evaluated in humans and caution is recommended in using acetylcholine solutions intracamerally in patients with already decompensated endothelium. Chondroitin sulfate, hydroxypropyl methylcellulose, and sodium hyaluronate are non-toxic to animal endothelial cells under conditions analogous to cataract extraction in humans but can be toxic to endothelium if there is continued contact with endothelium for hours. Chondroitin sulfate has been shown to have more of a protective effect in mechanical pseudophakos trauma probably because of its cohesiveness and tendency to coat the endothelium. Viscoelastics cause a significant rise in intraocular pressure of > 30 mm Hg in 3-10% of patients. Very high intraocular pressures are often seen postoperatively after viscoelastic use surgically in patients who preoperatively have a history of ocular hypertension or glaucoma.

Cell Count

The role of viscoelastics, cannulas, and irrigating solution additives in post-cataract surgery corneal edema: a brief review.

Corneal clarity is dependent upon maintenance of the corneal endothelial barrier and pump. Mechanical trauma is usually considered to be the most significant factor in corneal endothelial damage during cataract surgery resulting in postoperative corneal edema. However, corneal decompensation out of proportion to the degree of trauma seen during surgery does occur. These cases of unexpected corneal edema can often be traced to unrecognized preoperative endothelial dysfunction or to toxicity of intraocular medications used during surgery. This paper reviews the role of viscoelastics in reducing surgical trauma, their toxicity, and the risks of toxicity inherent in the use of re-usable cannulas and irrigating solution additives. Disposable cannulas should be used whenever possible. The use of re-usable cannulas with viscoelastics is highly likely to result in toxic residues being introduced onto the eye, and must be avoided. Irrigating solution additives should be tested with in-vitro human donor cornea perfusions prior to clinical use.

Cataract Extraction

Penetrating keratoplasty for pseudophakic bullous keratopathy after extracapsular cataract extraction.

Seventeen women underwent simple penetrating keratoplasty for pseudophakic bullous keratopathy after extracapsular cataract extraction. Corneal edema occurred an average of eight months after cataract surgery (range, zero to 32 months). Of 17 corneal grafts, 16 (94%) have remained clear during an average follow-up period of 14 months (range, two to 32 months). One eye had a nonimmunologic graft failure. Of 16 eyes with clear grafts, 14 (87%) achieved a visual acuity of 20/40 or better after surgery. Two eyes with a visual acuity of 20/50 and 20/200 had opacified posterior capsules and one demonstrated age-related macular degeneration. One eye with a postoperative visual acuity of 20/40 demonstrated cystoid macular edema. Fifteen of 17 contralateral eyes showed slit-lamp evidence of endothelial dystrophy.

Aged

Visual-field function in pseudophakia.

An automated perimeter (Octopus 2000) was used to examine visual-field function in 52 pseudophakic eyes. Threshold sensitivity was reduced throughout the visual field by from 0.4 to 20.0 decibels from that of threshold sensitivity in age-matched normal eyes. This reduction was comparable to that seen in contact-lens-corrected aphakic eyes.

Aged

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

Long-term survival of cryopreserved corneal endothelium.

Corneas of five patients who received cryopreserved penetrating grafts 15 years previously were evaluated by regional specular microscopy and computer-assisted morphometric analysis. This technique quantitates changes in cell size and shape as well as cell number. Comparisons were made with five eyes in four patients 15 years after penetrating keratoplasty utilizing fresh grafts. In three patients, fresh and frozen tissue were transplanted in the same host. These examinations showed no difference in structure or function comparing cryopreserved tissue with fresh donor tissue.

Cornea

Changes in the normal corneal endothelial cellular pattern as a function of age.

Human endothelial morphologic changes were quantitated by specular microscopy and computer-assisted morphometry to establish normal baselines of various morphologic parameters. Cellular polymegethism and cellular pleomorphism increases with age, and normal baseline parameters are detailed. Furthermore, no significant difference in any morphologic parameters between the right and left eye and between central and peripheral endothelium was detected in the normal corneas examined. These normal morphologic baselines can possibly be utilized to detect early corneal endothelial pathology and/or cell loss nondetectable by cell density measurement.

Adolescent

The effect of phenylephrine on the cornea.

Rabbit corneas were treated with three drops of phenylephrine hydrochloride with the epithelium intact or denuded. Corneal thickness was measured before and after drug treatment, and at various times after treatment the corneas were fixed for scanning and transmission electron microscopic observation. The results of this study show that phenylephrine caused a dramatic increase in corneal thickness (drug-induced edema) and cellular vacuolation within the keratocytes and endothelial cells in the corneas without the epithelium. Corneal thickness did not change and the ultrastructural changes were minimal following drug application in those corneas with the epithelium intact. Results of this study also suggest that phenylephrine has a cytotoxic effect on the corneal endothelium and keratocytes when used in corneas where the epithelium has been removed. In coreas with intact epithelium, the damage was less severe and limited to the epithelium.

Animals

Effect of phenylephrine on normal and regenerated endothelial cells in cat cornea.

Topical commercial phenylephrine HCl (Neo-Synephrine 10%) has been shown to cause an increase in corneal thickness and reversible vacuolization of corneal endothelial cells in rabbits. Using an in vivo model of regenerated corneal endothelial cells in the cat, we compared the cytotoxicity of phenylephrine-HCl 10% to regenerated and to normal, nonregenerated cells. Following removal of the epithelium, topical application of the drug causes the appearance of anterior and posterior bands of stromal edema and reversible vacuolization in both normal and regenerated endothelial cells. Phenylephrine was not more damaging to the regenerated cells. Polymorphonuclear leukocytes infiltrated between the regenerating cells 24 hr after treatment but did not appear to destroy them. Phenylephrine may therefore be implicated as a causative factor of corneal edema and postoperative inflammation.

Animals

Trifluridine in resistant human herpetic keratitis.

Patients with active dendritic herpetic keratitis that was unresponsive to topical idoxuridine or vidarabine therapy were treated topically with a 1% solution of trifluridine. The dendritic ulcers healed in an average time of 6.1 days. All patients tolerated the drug well except for one patient in whom a reversible crystalline epithelial keratitis developed.

Adolescent

Trephination of donor corneal buttons: a scanning electron microscopic study.

Corneal buttons were cut from cat and human donor eyes by anterior trephination (with or without scissor completion) and from excised corneoscleral rims by posterior trephination (with or without a press). Scanning electron microscopy was used to evaluate the slope and quality of the cut edge, the diameter of the section of Descemet's membrane that was actually cut, and the loss of endothelial cells around the cut edge. With anterior trephination, the diameter of the section of Descemet's membrane that is cut was found to be less than that of the trephine because the cut edge slopes inward. Posterior trephination with or without a press consistently produced circular buttons with accurately cut outward-sloping edges. This resulted in a diameter of Descemet's membrane which was greater than in the anteriorly trephinated buttons. There also was less damage to peripheral Descemet's membrane and endothelium with the posterior method, especially when compared to scissor cut buttons. A 360 degree peripheral ring of Descemet's membrnae (0.05 to 0.28 mm in width) was denuded of endothelial cells with all techniques.

Animals

Neurotrophic corneal ulcers in diabetes mellitus.

Three patients with juvenile-onset insulin-dependent diabetes mellitus had neurotrophic keratitis and/or ulceration presumably related to their diabetes. We suggest that significant neurotrophic corneal disease can occur in diabetic patients. The neurotrophic keratitis and corneal ulcers responded to treatment.

Adult

Comparative toxicity of intraocular irrigating solutions on the corneal endothelium.

Isolated rabbit and human corneas were perfused in vitro with Plasma-lyte 148 solution and with a glutathione bicarbonate Ringer's solution. The corneal swelling rate and ultrastructure were compared to corneas perfused with three commonly used intraocular irrigating solutions. Corneas perfused with Plasma-lyte 148 swelled at a rate of 47 mu/gr and the endothelial cells separated from each other and showed extensive damage after three hours of perfusion. By comparison, corneas perfused with 0.9% NaCl increased in thickness by 98 mu/hr, lactated Ringer's by 39 mu/hr, balanced salt solution by 24 mu/hr, and glutathione bicarbonate Ringer's solution by 4 mu/hr. These results indicate that endothelial cell damage and increased corneal thickness observed during perfusion was related to the incomplete composition of 0.9% NaCl, Plasma-lyte 148, and lactated Ringer's and that endothelial cell damage can be prevented if the intraocular irrigating solution contains concentrations of inorganic and organic constituents that are similar to those in aqueous humor.

Animals

Intraocular irrigating solutions. Their effect on the corneal endothelium.

The effects of several intraocular irrigating solutions on the corneal endothelium of rabbit and monkey corneas were evaluated, utilizing a specular microscope perfusion system with both scanning and transmission electron microscopy. Corneas perfused with 0.9% sterile isotonic physiological saline swell at a rate of 60mum to 90mum/hr; endothelial cells separate from each other and show extensive degenerative changes. Corneas perfused with lactated Ringer solution swell at a rate of 37mum to 40mum/hr, and the endothelial cells show slower, but progressive degeneration. Corneas perfused with balanced salt solution swell at 24mum to 31mum/hr, and degenerative changes become severe only after two hours. Corneas perfused with Ringer solution containing bicarbonate, reduced glutathione, and adenosine do not increase in thickness, and there is minimal deterioration of endothelial ultrastructure for periods of up to six hours.

Animals

Endothelial survival in corneal tissue stored in M-K medium.

Cat corneas were stored at refrigerator temperatures in M-K medium (TC-199, 5% dextran), modified M-K medium (TC-199, 1% chondroitin sulfate), or on the intact globe in moist chambers for intervals of one to nine days. Less than 5% of the endothelial cells stained with trypan blue in corneas stored one to four days, regardless of the method of storage. In contrast, after five days, 20% or more of the cells took up the stain in 17 to 21 corneas stored in M-K medium. Although stain uptake indicated nonviability of cells, most of the endothelial cells remained structurally intact when observed by scanning and transmission electron microscopy unless the corneas were incubated in fresh TC-199 for two hours at 35 degrees C before trypan blue staining. In that case, the percentages of disrupted cells observed at each time interval correlated with the percentages of cells that had stained in each cornea. These results indicated that storage in M-K medium did not extend the time donor coreas can be stored before transplantation beyond four days.

Animals

Keratomycosis in Wisconsin.

Candida albicans was the most common fungus responsible for mycotic keratitis in our series from a northern climate, as opposed to southern climates where other fungi were more common. Pimaricin was effective in our patients with Candida infections and in one patient with Aspergillus infection that had been unresponsive to previous amphotericin B.

Acetazolamide

Adenine arabinoside in idoxuridine unresponsive and intolerant herpetic keratitis.

Twenty-two patients with active herpes simplex dendritic keratitis, in whom topical idoxuridine was unsuccessful in controlling their disease, were treated with topical adenine arabinoside (ara-A), a purine analogue effective against many DNA viruses. This drug was an effective antiviral agent in these patients. No signs of ocular or adnexal toxicity were noted.

Adenine

Ara-A and IDU therapy of human superficial herpetic keratitis.

Ara-A ointment was compared to IDU ointment in patients with dendritic herpes simplex virus infection of the corneal epithelium. Twenty-eight patients were treated with Ara-A ointment and twenty-four with IDU ointment. The lesions healed in 5.1 days with Ara-A and in 6.9 days with IDU. This drug was given in a double-controlled manner, so that neither the patient, nor the investigator knew which drug the patient was receiving. The patient groups were comparable as to length of the dendritic lesion and duration of symptoms. The adverse reactions to each of these drugs were comparable and in no case was there any permanent ocular change from drug use.

Clinical Trials as Topic