Treatment of chronic blepharitis.
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Biomedical subjects
Publications and source records attributed to H M Leibowitz.
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The ability of suprofen, a nonsteroidal anti-inflammatory drug, and prednisolone acetate, a corticosteroid, to suppress polymorphonuclear leukocyte invasion of the rabbit cornea during an experimental keratitis was evaluated following topical ophthalmic administration of either drug alone or both drugs concurrently. Suprofen therapy initiated immediately after induction of inflammation was ineffective. However, if suprofen therapy was begun 48 hr prior to the induction of inflammation, the drug was effective. In contrast, prednisolone acetate therapy begun after the induction of inflammation was effective; 48 hr of pretreatment with the corticosteroid produced a marked increase in its therapeutic effect. When administered according to the same regimen, concurrent therapy with suprofen and prednisolone acetate was significantly more effective than treatment with either drug alone. This result was obtained irrespective of whether concurrent therapy was initiated prior to or after the inflammatory event.
The bioavailability in rabbit cornea and aqueous humor of an ophthalmic formulation of suprofen, a nonsteroidal anti-inflammatory drug, was evaluated following topical administration of a single dose to the eye. The drug penetrated rapidly into the uninflamed cornea with intact epithelium; highest levels occurred during the first 30 to 45 min after instillation and decreased thereafter. The bioavailability of suprofen in cornea and aqueous humor following administration of a 1.0% concentration was twice that produced by a 0.5% concentration of the drug. Topical application of multiple doses of suprofen failed to suppress polymorphonuclear leukocyte invasion of the cornea if treatment was started after the induction of inflammation. Suprofen therapy initiated prior to the induction of corneal inflammation and maintained into the post-inflammation period did produce a significant (P less than 0.01) decrease in the numbers of PMNs that invaded the inflamed cornea. There was no significant difference (P greater than 0.05) in the corneal anti-inflammatory effect achieved by the 0.5% and 1.0% concentrations of suprofen when administered according to this regimen.
We studied the effect of suprofen, a new ophthalmic nonsteroidal anti-inflammatory agent, on corneal wound healing. Nine-millimeter, central, perforating corneal wounds were made in albino rabbits and sutured with 10-0 nylon. The animals were randomly treated with balanced salt solution, suprofen vehicle, 1% suprofen, or 0.1% dexamethasone sodium phosphate administered topically for six days. On the seventh postoperative day, the sutures were removed and, in situ, the intraocular pressure was increased in a controlled manner until the wound burst. Dexamethasone applied four times a day significantly inhibited corneal wound healing, whereas suprofen given as often as hourly did not. Pretreatment with hourly administered suprofen for two days prior to surgery, in addition to the same postoperative hourly therapy, also did not significantly decrease stromal wound strength.
New Zealand albino rabbits received daily intraperitoneal injections of alcohol (ethyl alcohol), 1.6 g/kg and the effect of short-term (three days) and long-term (six weeks) administration on corneal inflammation was studied. Both regimens produced an average peak serum concentration of more than 0.200 g/dL, a level consistent with gross intoxication in the majority of humans. Clinical signs of intoxication were present in all animals, manifested by a gross disturbance of equilibrium and gait. Neither regimen produced measurable liver damage. Nonetheless, following both regimens of alcohol administration, significantly fewer polymorphonuclear leukocytes invaded the corneas of animals receiving alcohol than invaded the corneas of simultaneously run controls receiving intraperitoneal saline. These data provide a mechanism to explain why an alcoholic individual might not cope with a corneal infection as well as a nonalcoholic person, an observation long thought to be true clinically.
A 38-year-old man with brittle, juvenile onset diabetes mellitus and bilateral severe dry eyes with recurrent corneal ulcers developed atypical band-shaped calcifications of both corneas during a 24-hour period. Serum calcium, phosphate, and carbon dioxide levels all were within normal limits. The patient was mildly uremic but was not in renal failure. When EDTA chelation failed to clear the deposits, partial keratectomies were performed in both eyes and the specimens were examined by light and electron microscopy, including energy dispersive x-ray analysis. Microscopic studies revealed an atypical calcific keratopathy which involved neither Bowman's layer nor the most superficial stromal lamellae. The deposits were confined to deeper lamellae in the anterior stroma and by electron microscopy were composed of extracellular crystalline aggregates. Energy dispersive x-ray analysis of these aggregates confirmed the presence of calcium and phosphate. Corneal dessication appeared to be a major contributing factor in the rapid formation of these deposits.
The authors have developed an objective method for quantitation of herpes simplex virus in the corneal epithelium of rabbits. At appropriate times postinfection, full-thickness rabbit corneas were removed by trephination and subjected to one cycle of freezing and thawing. The corneal epithelium was then disrupted by sonication. The amount of infectious virus recovered from sonicated specimens was determined by an in vitro plaque assay, providing a measure of the quantity of virus present during the acute stage of herpetic keratitis. Using this technique, the authors found that the mean virus titer was reduced from 1.5 X 10(5) plaque forming units (pfu) per cornea in control rabbits to less than 200 pfu per cornea in rabbits treated topically for 2 days with 1% trifluridine. In contrast, instillation of 1% prednisolone acetate resulted in the persistence of higher levels of virus (275 pfu) than those observed in control rabbits (3 pfu) 4 days after the cessation of therapy.
Specular microscopic evaluation of rabbit, pig, and cat corneas was performed after storage in a moist chamber in McCarey-Kaufman (M-K) medium or in tissue culture medium 199. Irrespective of the storage method, cooling at 4 degrees C resulted in a deterioration of the specular microscopic image. Most of the changes proved to be reversible if the tissue was quickly rewarmed to 35 degrees C and maintained at that temperature for 20 minutes. One change, dark areas larger than a single cell, was not reversible and increased in prevalence with increased storage time. Trypan blue staining revealed that the dark areas seen with the specular microscope contained damaged endothelial cells. Deep corneal striae tended to increase as the storage interval increased, and considerable cell damage occurred in the endothelium covering these folds. Storage in M-K medium was the most effective of the three methods in preventing deep corneal folds and endothelial damage.
Sequential specular microscopy has shown that coalescence of endothelial cells occurs after thawing in cryopreserved rabbit corneas. Scanning electron microscopy of corneas studied in vitro by specular microscopy showed the same large, fused endothelial cells. As observed in the electron micrographs, these cells showed no evidence of the cell borders that had disappeared during the specular microscopic examination. These data support the reliability of our specular microscopic observations and provide additional evidence for the occurrence of fusion or coalescence of corneal endothelial cells.
Gel Tears, a clear, semisolid formulation of synthetic, high molecular weight, cross-linked polymers of acrylic acid, persists in the conjunctival sac for hours after topical instillation, slowly melting while absorbing fluid and retaining it locally. In the present study of 55 patients (106 eyes) with severe dry eyes, who were unable to obtain ocular comfort with frequent administration of a wide variety of commercially available artificial tear preparations, 78% were improved by Gel Tear therapy. Subjective symptoms such as burning, stinging, foreign body sensation, dryness, and photophobia were significantly (P less than 0.001) alleviated, while objective signs concurrently improved but to a lesser degree. No patient required Gel Tears more often than four times daily. Most maintained optimal comfort on a dose of twice daily or less, and several patients previously unable to obtain ocular comfort with hourly administered conventional artificial tears required Gel Tears less than once a day.
Intracellular structures probably representative of mitotic figures were seen by specular microscopy in the endothelium of a corneal graft following a rejection reaction. Serial measurements over an eight month period initially showed grossly enlarged cells and apparent mitotic figures. Subsequently, clusters of cells smaller than any cells previously seen were observed. Measurements of endothelial cell area over this period demonstrated a highly significant (P less than 0.0001) decrease in cell area, or increase in cell density, with time. These observations indicate that at least under some circumstances mitosis occurs in the endothelium of the adult human cornea.
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Specular microscopy of the corneal endothelium was performed on 16 eyes that had undergone corneal transplantation using cryopreserved donor material seven months to nine years previously. The average cell count was 817 cells/mm2 with a range of 360 cells/mm2 to 1808 cells/mm2. Grafts from donors under 30 years of age which had a very short death to freezing time showed a higher endothelial cell density than grafts from older donors with a longer death to freezing time. The most prominent findings were very large, multinucleated endothelial cells that are thought to be the result of cell fusion.
Separate, randomized, double-masked clinical studies were conducted to determine the therapeutic efficacy of fluorometholone acetate, a new ophthalmic corticosteroid formulation, in suppressing external ocular inflammation (conjunctivitis, episcleritis, scleritis). Fluorometholone acetate 0.1% was compared to fluorometholone 0.1%, and the acetate formulation was found to be significantly (p = 0.03) more effective. Fluorometholone acetate 0.1% also was compared to prednisolone acetate 1.0%; there was no significant difference (p = 0.49) between these two corticosteroids in their ability to suppress external ocular inflammation. It appears that alteration of fluorometholone from its alcohol base to its acetate derivative changes the drug from a moderately effective to a highly effective anti-inflammatory agent.
The corneal endothelium of a 71-year-old woman with iridocorneal endothelial syndrome had two types of cell structure and density demonstrated by specular microscopy. In parts of the central cornea, characterized by normal endothelium on examination with the slitlamp biomicroscope, a substantial increase in cell density over that in the opposite normal eye was observed. In other focal areas of the central cornea, characterized by a typical beaten-silver appearance on slit-lamp biomicroscopy, considerable cell loss and cellular pleomorphism were observed in comparison with the surrounding normal-appearing endothelium. Nevertheless, the endothelial cell density in these areas was not significantly greater than that of the opposite uninvolved eye. This finding supports the theory that endothelial proliferation in this disease occurs not only on the iris but also in the endothelial cell layer of the cornea.
In the rabbit, cells coalesce to repair a damaged corneal endothelial layer. Clinical specular microscopy showed that this phenomenon also occurs in human beings. The resulting endothelial cells are large, irregularly shaped, and multinucleated. They are quite different in their specular microscopic appearance from corneal endothelial cells seemingly undergoing mitosis, which was observed in a successful penetrating keratoplasty and which represents another apparent mode of repair. Additional evidence for coalescence of endothelial cells is derived from evaluation of histograms of cell size v age that have been published previously.
After thawing, cryopreserved rabbit corneas were stained with trypan blue and cellular damage was evaluated with the specular microscope using indirect illumination. Thereafter, the cornea was maintained at 35 degrees C, and specular microscopy, performed from the endothelial side, was used to observe the same area of endothelium for several hours. Dead endothelial cells interfered with specular reflection and appeared as dark areas devoid of cellular definition. Viable cells, presumably damaged by freeze-thaw injury, began to effect repair within one hour after thawing and coalesced to form a single larger cell. Our photographic evidence suggests that coalescence of injured corneal endothelial cells represents an important step in the early repair process, resulting in a reduction of the total number of cells but enabling damaged cells to survive.