[Endothelial microscopy examinations after short-term storage of animal corneas].
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Biomedical subjects
Publications and source records attributed to H M Leibowitz.
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Hourly topical administration of 0.1% fluorometholone acetate ophthalmic suspension produced, on the average, a 47% reduction in the polymorphonuclear leukocytes invading the cornea during an experimentally induced inflammatory keratitis. This is a significantly greater anti-inflammatory effect than we have previously reported for the alcohol derivative of fluorometholone and is not significantly different from the therapeutic effect of 1.0% prednisolone acetate ophthalmic suspension, the most effective corneal anti-inflammatory agent that we have studied to date. Fluorometholone acetate (0.1%) formulated as a high-viscosity carbomer gel and applied at three-hour intervals reduced invading leukocytes in the cornea an average of 48%, an effect not significantly different from hourly administration of the suspension.
The intraocular pressure response to topically instilled 0.25% betaxolol hydrochloride was evaluated in 12 patients with chronic open angle glaucoma or ocular hypertension. The drug produced a significant lowering of IOP in all 12 of the patients under study. A 30% to 35% decrease below baseline IOP was observed and was maintained during the one-year observation period. Visual acuity was stable in all subjects throughout the study and corneal anesthesia was not encountered. Tear secretion was not adversely effected by betaxolol, nor did topical administration of the drug produce any systemic cardiovascular response of consequence. Blood pressure and pulse rate remained stable throughout the year. These data suggest that an ophthalmic formulation of betaxolol may have substantial clinical potential for the treatment of glaucoma.
The progressive morphological changes of cornea guttata in Fuchs' endothelial dystrophy have been characterized by clinical specular photomicroscopy. Five specific stages in the development of excrescences can be discerned using this in vivo technique. Several stages can be observed in the same cornea at a given time, although in most cases the majority of guttate changes seemed to have progressed to the same stage of development. All five stages of cornea guttata discerned in this study can occur in a cornea clinically free of edema. Two types of cornea guttata can be identified in vivo. One has a smooth, regular posterior surface, whereas the posterior contour of the second is irregular.
Aphakic eyes, some with edematous corneas, and others with corneas free of edema, but all with formed vitreous humor in contact with the corneal endothelium, were studied. Removal of vitreous humor from the anterior chamber by closed vitrectomy resulted in substantial improvement in the state of corneal hydration and, in some cases, in the elimination of clinically notable corneal edema. Specular microscopy showed endothelial abnormalities in the edematous corneas that were not present in corneas with vitreous contact that remained free of edema. However, those endothelial changes seen in edematous corneas before vitrectomy seemed to persist after vitrectomy and corneal deturgescence. Thus, elimination of vitreous contact may result in clinical reversal of corneal edema despite a prolonged period of vitreous contact and in the face of seemingly irreversible endothelial changes.
The in vivo antibacterial effectiveness in the rabbit cornea of several antibiotics delivered by topical application, by periocular injection, and by intravenous (IV) inoculation was determined against Staphylococcus aureus and Pseudomonas aeruginosa. Topical instillation of antibiotic was highly effective in eliminating these organisms from the cornea. In contrast, despite a considerable increase in the quantity of antibiotic administered, we could demonstrate no statistically significant reduction in the number of viable staphylococcal or Pseudomonas organisms in the cornea when the antibiotic was given by periocular or by IV injection.
Prednisolone acetate was formulated in a high-viscosity carboxypolymethylene gel at concentrations of 0.125% and 1.0%. The ability of these gel preparations to suppress inflammation in the cornea was assessed and compared with the antiinflammatory capabilities of conventional commercially available prednisolone acetate ophthalmic suspensions. When administered hourly, the gel formulations produced no greater anti-inflammatory effect than the conventional suspensions. However, the gel formulations were equal in effect to the suspensions and maintained their effects considerably longer than did the suspensions. When applied at intervals up to and including four hours, there was no falloff in effect; the gel demonstrated a level of anti-inflammatory effectiveness that could not be distinguished from hourly administration of the suspension.
A double-masked randomized study was conducted at four centers to compare the efficacy and safety of tobramycin and gentamicin ophthalmic ointment in the treatment of superficial external eye disease. Seventy-seven patients with blepharitis and/or conjunctivitis were evaluated for safety, and 56 of the 77 individuals also qualified for evaluation of drug efficacy. After a 10 day treatment regimen, 97% of the tobramycin treated patients and 91.3% of the gentamicin treated patients were clinically cured or improved. Antibacterial effectiveness studies in the conjunctiva showed that tobramycin eradicated or controlled 87.8% of the bacterial infections vs. 77.4% for gentamicin. There was also a 9.3% adverse reaction rate with tobramycin vs. 17.6% with gentamicin. Primary symptoms consisted of erythema, injection, discomfort and itching. All adverse reactions were mild and cleared upon discontinuation of the study drug. While the trends seem to favor tobramycin, no difference was statistically significant at the p less than or equal to 0.05 level. These results indicate that tobramycin is a clinically effective and safe topical antibiotic and that it is comparable to gentamicin for topical treatment of bacterial external eye infections. It also may be better tolerated than gentamicin.
Anterior uveitis was produced in the rabbit eye by introducing a standardized clove oil globule into the anterior chamber. The response was characterized by an increase in the vascular permeability of the anterior uveal tract, resulting in the exudation of protein and the migration of leukocytes into the anterior chamber. Using radiolabeled agents and couting techniques, protein and cells in the aqueous humor were measured, providing an objective, quantitative assessment of the severity of inflammation in the anterior chamber. Frequent topical administration of 1.0% prednisolone acetate during the first 100 hours of the experimental anterior uveitis produced a significant decrease both in protein and in the number of leukocytes in the anterior chamber.
The effect of a topically administered corticosteroid, 1.0% prednisolone acetate, on bacterial replication in rabbit cornea receiving adequate antibiotic therapy was determined. Staphylococcus aureus keratitis was treated either with neomycin sulfate or gentamicin sulfate, while Pseudomonas aeruginosa keratitis was treated either with gentamicin or polymyxin B sulfate. Each antibiotic was administered topically at hourly intervals in both the commercially available concentration and as a formulation containing four times the quantity of drug found in the commercial preparations. In each instance, the antibiotic regimen sharply reduced the number of viable organisms in the cornea, although the concentrated preparations did so more rapidly and effectively. The addition of 1.0% prednisolone acetate had no measurable effect on outcome. In no instance was there a statistically significant difference between number of residual viable organisms in antibiotic-treated corneas and antibiotic/corticosteroid-treated corneas.
The ability of the cornea to react to inflammatory stimuli is limited, and in most instances the polymorphonuclear leukocyte is primarily responsible for corneal damage. Of currently available drugs, corticosteroids are the most effective for the non-specific control of these inflammatory cells. Principles for obtaining maximal therapeutic effect from minimal amounts of the drug are presented. The use of corticosteroids in the treatment of a keratitis caused by various types of replicating microbial agents is discussed. The response to therapy of inflammatory processes in the conjunctiva seemingly differs from the response in the cornea. Suggestions are offered for corticosteroid use in conjunctivitis.
Corticosteroids are by far the most frequently used agents to treat ocular inflammation. When administered topically to the eye, different derivatives of the same corticosteroid base are not equivalent in their antiinflammatory properties. A change in the derivative of a corticosteroid base alters its behavior as an antiinflammatory agent. To date, the acetate derivative of each corticosteroid base studied has been the most effective, and among commercially available ophthalmic formulations, 1.0 percent prednisolone acetate is the drug of choice for maximal antiinflammatory effect. Hourly instillation produces a greater, more rapid reduction of corneal inflammation than does instillation of the drug every 4 hours, while instillation at 15-minute intervals results in an even greater therapeutic effect. Topical delivery of five doses of 1.0 percent prednisolone acetate at 1-minute intervals each hour results in an antiinflammatory effect comparable to that achieved by instillation every 15 minutes. Topical instillation of a corticosteroid produces a greater reduction in inflammatory cells invading the cornea than does periocular injection of a steroid. Administration of corticosteroids concurrently by topical and subconjunctival routes produces an additive antiinflammatory effect. Addition of a topically applied corticosteroid to an effective topical antibiotic regimen containing a bactericidal agent does not enhance bacterial replication in the cornea if the corticosteroid is not instilled more frequently than the antibiotic. Corticosteroids enhance viral proliferation and are contraindicated in active epithelial herpetic keratitis. Many instances of stromal herpetic keratitis appear to be a toxic or immune response to incomplete, nonreplicating viral particles rather than alteration of tissue by multiplying live virus, and the judicious use of corticosteroids is advocated along with an antiviral antimetabolite. Because control of replicating fungal organisms by specific antifungal agents is often difficult to achieve, corticosteroids should not be used in the treatment of mycotic keratitis.
The in vivo antibacterial effectiveness in the rabbit cornea of several commercially available ophthalmic antibiotic preparations was determined against a single strain of Pseudomonas aeruginosa isolated from a human corneal ulcer. Each antibiotic was instilled topically at hourly intervals, and the number of residual viable organisms in the cornea subsequently was ascertained. In vivo measurements correlated well with in vitro data and with generally held clinical impressions. Three antibiotics, gentamicin sulfate, polymyxin B sulfate, and colistin sulfate, suppressed corneal growth of P aeruginosa in commercially available concentrations. Gentamicin was slightly more effective than polymyxin B; both drugs were substantially more effective than colistin. Formulations of gentamicin and polymyxin B containing approximately four times the quantity of drug found in commercial preparations eliminated this P aeruginosa strain from the cornea much more rapidly than did the commercial preparations.
The clinical specular microscope yields a corneal endothelial image. Depending on the slit width of the illumination source, a typical endothelial photomicrograph contains three or four distinct zones. The appearance of the boundary between the endothelial cell pattern and the adjacent dark zone, called the dark boundary, reflects the configuration of the endothelial cell-aqueous humor interface and provides important information about the posterior corneal surface.
The clinical specular microscope shows the morphological appearance of the endothelium in normal and abnormal corneas. This instrument resolves the endothelial mosaic of the normal cornea into a quasiregular pattern of contiguous cells having well-defined cell boundaries. Cell size varies over a wide range in a number of disorders, and endothelial cells may assume shapes that are substantially different from their usual hexagonal appearance. Cell boundaries are dark and most commonly appear as a straight, narrow line. However, other types of cell boundaries, collectively referred to as doubled boundaries, have been encountered. Cell boundaries normally intersect in a manner that results in three angles of intersection, each approximately 60 degrees, but variations from this pattern are seen. A number of noncellular structures also can be seen in the endothelial zone.
The corneal endothelium in 12 cases of keratoconus was examined with the clinical specular microscope. There appeared to be an increase in cellular pleomorphism with many cells considerably smaller than normal distributed throughout the endothelial cell population. There were also many large, elongated cells whose long axis showed a definite tendency to assume a similar directional orientation. The long axis of these cells seemed oriented toward the apex of the cone, and the cells appeared to have been stretched by the ectatic process. Many endothelial cells contained dark intracellular structures. Their significance is unknown. The single cornea in this series with a history of acute hydrops contained a localized area in which the endothelial cells were seven to ten times larger than normal. This suggests that rupture of the endothelium and Descemet's membrane, responsible for the acute edematous process, occurs at this site, and that the adjacent cells enlarged to fill the defect.
Four patients, each of whom had had an uncomplicated cataract extraction, were examined because of an apparent epithelialization of the anterior chamber. In each instance, the diagnosis was later verified histopathologically. The involved eye was photographed with the clinical specular microscope and the endothelial photomicrographs were analyzed. It was noted that considerable endothelial cell loss had occurred, as evidence by the larger size of the remaining cells. Endothelial cells were present but they were grossly abnormal well below the demarcation line visible with the slit-lamp biomicroscope. These in vivo observations support the thesis that damage to the corneal endothelium is a necessary factor for epithelial invasion of the anterior chamber.
The relationship between the frequency with which 0.125% and 1.0% prednisolone acetate ophthalmic suspensions are instilled and the anti-inflammatory effect they achieve in the cornea was studied. Within the time limits of the experimental protocol, application of the drug at four-hour intervals failed to produce an effect while hourly administration of both concentrations of the corticosteroid produced a substantial anti-inflammatory effect. Instillation at 15-minute intervals resulted in a significantly (P less than .05) greater reduction of the polymorphonuclear leukocytes invading the cornea than did administration of the medication every hour. If five doses of prednisolone acetate were applied topically at one-minute intervals each hour, both concentrations of this corticosteroid produced a therapeutic effect in the cornea equal to that achieved by administration of the drug every 15 minutes.