Irving H. Leopold

A Clinical Evaluation of the Effects of Topically Applied Levobunolol and Timolol on Increased Intraocular Pressure

Data from two short-term double-masked studies using 24 and 16 subjects suggest that topically applied levobunolol safely and effectively treats open-angle glaucoma and ocular hypertension. The onset of effect of a single drop of 0.5% levobunolol occurred within the first hour, producing a maximal hypotensive effect of more than 8 mm Hg after two hours. An intraocular pressure deceased of greater than or equal to 2 mm Hg was still observed after 24 hours for both concentrations of levobunolol tested (0.5% and 1%). Intraocular pressure decreases of more than 9 mm Hg persisted during a one-month trial in which patients were treated twice daily, confirming the results obtained in the 24-hour study. Systemic effects of both timolol (0.5%) and levobunolol (0.5% and 1%) included a consensual intraocular pressure-decreasing effect in the untreated eye and clinically significant reductions in heart rate. Diastolic blood pressure was decreased at two and four hours after administration of 0.5% levobunolol.

The Influence of Systemic Drugs on Tear Constituents

Tears of patients and laboratory animals on systemic medications have been analyzed for the presence and influence of these agents on tear constituents. Antibiotic penetration into tears, drugs stimulating or retarding lacrimation, and effects on tear electrolytes, lysozyme, and immunoglobulins are reviewed from the literature. Important applications to clinical practice such as contact lens wear, general anesthesia, eye infections, and epiphora or dry eye symptoms are discussed.

Ocular Hypotensive Action of Labetalol

Labetalol has a unique and profound effect on the IOP of rabbits, in contrast to pure beta-adrenergic blockers which have little or no effect in this animal. Its action cannot be satisfactorily explained by simple alpha and beta-adrenergic blocking activity. In the concentrations used, it failed to block the action of a beta-adrenergic agonist (isoproterenol), the action of an alpha-adrenegic agonist (norepinephrine), and its own hypotensive action was neither blocked nor potentiated by the alpha-adrenergic blocker phenoxybenzamine. However, the beta blocker, timolol, did reduce the action of labetalol. These observations and the reduced response to labetalol after cervical sympathectomy, suggest that labetalols ocular hypotensive effect may occur through some mechanism other than alpha or beta blockade.

Excretion of Salicylic Acid into Tears Following Oral Administration of Aspirin

The concentration of salicylic acid in human tears has been measured by using reverse-phase, high-pressure liquid chromatography. Pharmacokinetic profiles in tears and in plasma have been obtained following oral administration of 650, 1300, and 1950 mg of aspirin in normal subjects. Salicylate excretion in tears is dose-dependent and is proportional to the plasma concentration. Tear and plasma salicylate levels for rheumatology patients on salicylates are also included.

Noncorticosteroidal anti-inflammatory agents in Ophthalmology.

Efforts have been made to develop noncorticosteroidal anti-inflammatory therapy. The goals of such therapy have been to eradicate the primary cause, prevent the initial tissue injury, moderate inflammatory response, and enhance tissue repair while minimizing and eliminating the undesirable aspects of the therapy.

Antiproteolytic Activities Found in Human Tears

Human tears were found to inhibit the thiol-dependent protease, papain. Inhibitory activity in normal tears was compared with that in patients with blepharitis, infectious and allergic conjunctivitis, and herpes simplex. Activities lower than normal were found in some patients with infectious conjunctivitis and blepharitis. Higher than normal activities were found in patients with herpes simplex and allergic conjunctivitis. Differences from normal values were found to be statistically significant in allergic conjunctivitis and blepharitis by analyses of sample medians, means, and geometric means. A function of this inhibitor in external ocular inflammations is suggested.

Update on antibiotics in ocular infections.

Each year, new antimicrobials are found or synthesized in an effort to improve the chance of overcoming infections. In the early 1950s, the only antibiotic available for ocular use was penicillin. Today, ophthalmologists can make a choice from a large selection of antibiotics for ocular infections. The majority of antibiotics have been literally unearthed, since worldwide soil surveys may have been the means of their discovery. In addition, synthetic derivatives of penicillin, cephalosporins, aminoglycosides, and tetracyclines, as well as drugs against tuberculosis and fungi, have become available, and new names have been added to the already bewildering list of less frequently used sulfonamides. However, it takes several years to appreciate the impact of new agents and the continued contribution of older ones. Constant reevaluation is mandatory. The real benefits as well as the untoward effects of a new antimicrobial agent may not be known until several years after the clinical introduction. In addition to approaching infection from the viewpoint of the offending organism and a specific antibiotic to address this organism, one may also approach this problem from the hosts immunity. Until now, we have relied largely on the corticosteroids, but one must also consider various nonsteroidal anti-inflammatory agents and, even more importantly, the development of drugs to enhance the hosts natural immunity.

Clinical Immunology in Ophthalmology: The 1975 Bedell Lecture Irving

Immunology has played a recognizable role in ophthalmology for many years. The old immunology concerned itself with antibodies, skin tests, complement, agglutinins, precipitants, and lysins. The old immunology was responsible for the remarkable development of vaccines, vaccinations, antisera, and the prophylactic use of toxins. The new immunology cannot display such achievements as yet. However, continued study in this area could lead to significant improvements in diagnosis, prognosis, and the development of effective immunoregulants in inflammatory and neoplastic disease.