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Biomedical subjects

H M Leibowitz

Publications and source records attributed to H M Leibowitz.

At least 73 records · Page 4Linked to original sources

External ocular toxicity of dipivalyl epinephrine.

Of 26 patients enrolled in a study designed to assess the usefulness of dipivalyl epinephrine 0.1%, administered topically at 12-hour intervals, for lowering intraocular pressure in patients with glaucoma and ocular hypertension, six patients (23.1%) developed adverse external ocular side effects severe enough to require that the drug be discontinued. Four of these six patients had a history of previous intolerance to epinephrine. The other two had successfully used epinephrine HCl 2% for more than two years before being treated with dipivalyl epinephrine and developed an adverse reaction after taking the drug 18 and 22 months, respectively. One patient with a history of epinephrine intolerance has successfully used dipivalyl epinephrine for 26 months to date. Our observations suggest that duration of exposure is an important factor in the development of sensitization to topically applied dipivalyl epinephrine.

Administration, Topical↗

Evaluation of dexamethasone acetate as a topical ophthalmic formulation.

Penetration of an ophthalmic suspension of 0.1% dexamethasone acetate into the rabbit cornea and aqueous humor was unaffected by the status of the corneal epithelium or by the presence or absence of intraocular inflammation. However, the total quantity of this corticosteroid that could be measured in the cornea or aqueous humor was significantly less than that produced by either dexamethason alcohol or dexamethasone sodium phosphate. Despite this, dexamethasone acetate was the most effective of the three dexamethasone derivatives in suppressing inflammation in the cornea, which indicates that following topical administration to the eye it is the most potent of the dexamethasone derivatives studied. This greater therapeutic effect does not seem to be accompanied by a greater propensity to increase intraocular pressure. Comparison of the intraocular pressureincreasing effect in known corticosteroid responders of dexamethasone acetate with that of dexamethasone sodium phosphate, the least effective of the dexamethasone products studied, demonstrated no difference between the two drugs. These data support the conclusion that dexamethasone acetate is superior to the commercially available dexamethasone derivatives for use as a topical ocular anti-inflammatory agent.

Animals↗

Prevalence of senile cataract, diabetic retinopathy, senile macular degeneration, and open-angle glaucoma in the Framingham eye study.

Of the Framingham, Massachusetts Heart Study population, 2,675 individuals underwent an ophthalmologic evaluation that stressed detection of senile cataract, diabetic retinopathy, open-angle glaucoma, and senile macular degeneration. Those examined were 52 to 85 years old at the time this study was initiated. The prevalence rate of each of these ocular conditions increased with age. Prevalence of senile cataracts ranged from 4.6% for those between the ages of 52 to 64 years to 46% for those 75 to 85 years of age. Diabetic retinopathy was present in 2% of those between 52 and 64 years of age or older. Overall prevalence of senile macular degeneration was 9%, with a prevalence rate of 2% in our youngest age group and 28% in the oldest age group. Open-angle glaucoma had an overall prevalence of approximately 3%. This disease also showed a statistically significant (P less than .01) increase with age from 1.4% (52 to 64 years old) to 7.2% (75 to 85 years old).

Aged↗

Periocular injection of corticosteroids: an experimental evaluation of its role in the treatment of corneal inflammation.

The present experiments demonstrate that subconjunctivally injected corticosteroids are less effective in suppressing corneal inflammation than are topically instilled corticosteroids. Topical administration of 6.5 mg of prednisolone acetate over a 30-hour period reduced corneal inflammatory activity by 52%. Subconjunctival injection of 50 mg of the same steroid, also given over a 30-hour period, yielded a 15% reduction in corneal inflammation. A fourfold increase (200 mg) in the quantity of prednisolone acetate injected subconjunctivally resulted in a nonsignificant (P less than .05) increment (24%) in anti-inflammatory effect. Dexamethasone sodium phosphate achieved a 30% reduction in corneal inflammation, the maximum effect observed after subconjunctival administration. The data suggest that different modes of corneal penetration are involved after drug delivery via the two routes. Concurrent administration of corticosteroids by the topical and subconjunctival routes seemingly produced an additive anti-inflammatory effect.

Administration, Topical↗

Drug interaction in the eye. Concurrent corticosteroid-antibiotic therapy for inflammatory keratitis.

Concurrent instillation of individual preparations of a corticosteroid and an antibiotic resulted in significantly (P less than .05) lower peak corneal and aqueous humor steroid levels than those achieved by the steroid alone. Both the interval elapsing between instillation of the two drugs and the sequence in which they were administered influenced subsequent steroid bioavailability. Corticosteroid levels in the cornea after administration of a combination steroid-antibiotic preparation were not significantly different (P less than .05) from those detected after instillation of the same steroid alone, suggesting that, for the treatment of corneal disorders, use of a combination preparation may offer a method to circumvent certain drug interactions. The decrease in ocular steroid bioavailability could not be directly equated with differences in antinflammatory effectiveness, so that the therapeutic relevance of the demonstrated drug interaction is not known.

Adrenal Cortex Hormones↗

Topical antibiotic therapy of staphylococcal keratitis.

The in vivo antibacterial effectiveness in the rabbit cornea of a number of commercially available ophthalmic antibiotic preparations was determined against a single strain of penicillinase-producing Staphylococcus aureus 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 demonstrated that five antibiotics--neomycin sulfate, gentamicin sulfate, erythromycin, tetracycline hydrochloride, and chlortetracycline hydrochloride--were equally effective in suppressing growth of the strain of S aureus studied. Therapeutic results were the same whether the corneal epithelium was present of absent for each of the drugs studied. With one exception (chloramphenicol), there was excellent correlation between in vivo and in vitro findings.

Administration, Topical↗

Penetration of topically administered prednisolone acetate into the human aqueous humor.

A single standardized drop of 1.0% prednisolone acetate labeled with tritiated thymidine was administered topically to one eye of 58 patients shortly before elective cataract extraction. An aqueous humor sample was aspirated at varying intervals and its corticosteroid content was determined. Peak drug concentration in aqueous humor was 1.13 mug/ml, which occurred 30 to 45 minutes after instillation of the medication. Substantial quantitites of corticosteroid were found in the aqueous humor five minutes after drug administration. The area under the drug concentration in aqueous humor-vs-time curve (a measure of the drug's bioavailability in aqueous humor) was 88 mug min/ml, and its half-life in human aqueous humor was 28 minutes. None of these values were significantly different from the comparable values in rabbit eyes.

Adult↗

The Framingham Eye Study. I. Outline and major prevalence findings.

During the period 1973--1975, 2675 out of 3977 still-living members of the Framingham, Massachusetts, study population, who have been under investigation for coronary disease risk factors since 1948 and who were in 1973--1975 aged 52 to 85, were given an eye examination stressing cataract, diabetic retinopathy, macular degeneration and glaucoma. Of 2940 subjects who still lived in the local Framingham area, 2477 were examined. Local population prevalence for one or both eyes positive was: 15.5% for senile cataract, 3.1% for diabetic retinopathy, 8.8% for senile macular degeneration and 3.3% for open-angle glaucoma. The proportion of adults with poor "best" visual acuity may be much less than has been estimated by the National Health Survey and the proportion with open-angle glaucoma much more than currently suspected on the basis of foreign studies.

Age Factors↗

The Framingham Eye Study. II. Association of ophthalmic pathology with single variables previously measured in the Framingham Heart Study.

Using the age-sex-specific data collected in the Framingham Heart Study 1948--1964 together with ophthalmic diagnoses made in the Framingham Eye Study in 1973--1975, the following variables were found to be associated with senile cataract: education, casual blood sugar, systemic blood pressure, height, vital capacity, serum phospholipid and hand strength; with senile macular degeneration: systemic blood pressure, height, vital capacity, left ventricular hypertrophy, hand strength and history of lung infection; with diabetic retinopathy: casual blood sugar, urine sugar and other specific elements of diabetes; with ocular hypertension: systemic blood pressure, height, casual blood sugar and pulse rate. No variables were identified as associated with open-angle glaucoma. The paper stresses the need for corroboration of these findings, which may be a mix of real and chance associations, and the need for additional analyses before any of these associations are considered evidence of factors related to risk of ophthalmic disease.

Aged↗

Kinetics of topically administered prednisolone acetate. Optimal concentration for treatment of inflammatory keratitis.

Two types of quantitative measurements were made in rabbit corneas. First, the level that varying concentrations of topically administered prednisolone acetate attained in the cornea and aqueous humor was determined. Then, the ability of varying concentrations of this corticosteroid to suppress corneal inflammation was ascertained. The maximum dose-response curve for anti-inflammatory effect in the cornea was achieved by the 1.0% concentration, the highest concentration commercially available. Higher concentrations permitted greater quantities of the drug to gain access to the cornea and aqueous humor but produced no measurable increment in anti-inflammatory effect. These experimental observations suggest that concentrations of prednisolone acetate higher than 1.0% have an increased potential for toxicity without offering additional therapeutic benefit.

Administration, Topical↗

Human conjunctivitis. II. Treatment.

One hundred forty-three patients (207 eyes) with conjunctivitis or blepharoconjunctivitis were investigated to determine (1) the safety of topical corticosteroid therapy and the relative efficacy of formulations of increasing potency and (2) the effectiveness of a steroid-antibiotic preparation compared to each of its components alone and to a placebo. The corticosteroids were equally effective in suppressing conjunctival inflammation; all were more effective than the placebo. Active conjunctivitis was controlled more readily by those preparations containing a steroid, both alone and in combination. The corticosteroid alone (dexamethasone) was more effective in producing inactivation of conjunctivitis than the antibiotic alone ( a mixture of neomycin sulfate and polymyxin B sulfate). This observation remained unchanged when cases of Staphylococcus aureus conjunctivitis were analyzed separately. No serious complications resulted from any treatment regimen.

Administration, Topical↗

Quantitation of bacterial infection and antibiotic effect in the cornea.

We report an experimental model that allows objective quantitation of bacterial keratitis. The model permits direct measurement of the number of viable organisms in the cornea after varying periods of in vivo growth. The size of the inoculum used to produce the corneal infection is critical, and the experimental organism must be standardized for its growth characteristics in the cornea. The end point is an objective one, productive of numerical data that can be subjected to statistical analysis. The findings are highly reproducible and the system is sufficiently sensitive to indicate the ability of a topically administered antibiotic to reduce the number of viable organisms in the cornea of an outbred rabbit population.

Administration, Topical↗

Morphological changes in corneal endothelial cells after penetrating keratoplasty.

Fifteen patients who had had a successful penetrating keratoplasty were photographed with the clinical specular microscope and the resulting endothelial photomicrographs were analyzed. The average endothelial cell area was one to six times larger and the average endothelial cell perimeter was one to 2 1/2 times larger than that of a normal cornea of a subject the same age as the donor. In each corneal graft, endothelial cell areas and perimeters clustered tightly around a mean value, although the mean value for different corneas varied significantly. The thickness and transparency of each graft was normal, indicating that within the observed limits the success of the transplantation procedure did not depend on final endothelial cell size or perimeter.

Cornea↗

Biological equivalence of ophthalmic prednisolone acetate suspensions.

We compared both concentrations (0.125 and 1.0%) of two widely used commmerical brands of prednisolone acetate suspensions. We investigated the concentration that each product attained in the cornea and aqueous humor, and each product's anti-inflammatory effectiveness in the cornea. There was no statistically significant difference in the corticosteroid levels measured in cornea or aqueous humor after administration of the two suspensions. Similarly, there was no significant difference in the ability of the two commercial preparations to suppress corneal inflammation.

Acetates↗

In vivo photomicrography of the corneal endothelium.

A technique and apparatus for observing and photographing the corneal endothelium in vivo at a magnification of approximately times 200 is described. The method is suitable for animal experimentation and for diagnostic observation and clinical research in humans.

Aging↗

Penetration of fluorometholone into the cornea and aqueous humor.

In each of the experimental conditions studied, fluorometholone penetrated into the cornea and aqueous humor following topical administration of a standard drop. The amount of drug measured in each location was less than that previously documented for dexamethasone and prednisolone preparations. In contrast to these more conventional steroids, the ocular penetration of fluorometholone appeared to be unaffected by the presence or absence of the corneal epithelium or of intraocular inflammation.

Administration, Topical↗