William P. Boger

Long-term experience with timolol ophthalmic solution in patients with open-angle glaucoma.

Timolol was used by 37 glaucoma patients from 1 to 18 months. Of those 37 patients, 31 used timolol for three months or longer and 7 used timolol for over one year. Timolol produced sustained reductions in intraocular pressure with continuous administration and did not induce miosis, accommodative spasm, or other annoying side effects. Systemic absorption produced a mild slowing of resting pulse rate. In some patients, timolols ocular hypotensive effects are additive to miotics and carbonic anhydrase inhibitors.

Clinical Trial Comparing Timolol Ophthalmic Solution to Pilocarpine in Open-Angle Glaucoma

A ten-week, double-masked, randomized, clinical trial compared timolol ophthalmic solution and pilocarpine in the therapy of open-angle glaucoma. Timolol decreased the intraocular pressure at least as much as pilocarpine and did not induce miosis, accommodative spasm, or other annoying side effects. The pulse was slowed by timolol, but blood pressure was unaffected. Significant decreases in intraocular pressure were still present after ten weeks of maintenance therapy with the same concentration of drug.

The beta-adrenergic blocking agents and the treatment of glaucoma

The autonomic nervous system is divided into the parasympathetic and sympathetic systems, with three types of adrenergic receptors: alpha (smooth muscle contraction), beta1 (cardiac acceleration and fatty acid mobilization) and beta2 (smooth muscle relaxation). Substances affecting the function of the adrenergic system are the agonists or stimulators, which mimic the effects of endogenous norepinephrine or epinephrine, and antagonists or blockers, which block the receptors and prevent stimulation by the agonists. Autonomic stimulation in the eye mediates various changes which apparently affect outflow facility and rate of formation of aqueous humor. Alteration of either or both of these factors by autonomic agonists or antagonists may have a direct or an indirect effect on intraocular pressure. Beta-adrenergic blocking substances have been used to treat a variety of diseases. Some of the effects of these drugs are attributable to properties other than beta blockade, such as intrinsic sympathomimetic activity and local anaesthetic activity. Side effects of this class of drugs require caution in cases of congestive heart failure and in asthmatics. Autonomic agents used in the treatment of ocular hypertension and glaucoma include pilocarpine, a chilinergic agonist, epinephrine, an adrenergic agonist, and various beta adrenergic blockers or antagonists including propranolol, atenolol and timolol. The physico-chemical properties and pharmacokinetics of timolol are reviewed. Data showing a significant reduction in intraocular pressure as a result of ocular instillation of timolol are presented. Reduction of the rate of aqueous formation appears to be the mechanism of action. A low incidence of non-serious side effects is reported.

Phenylephrine Provocative Testing In The Pigmentary Dispersion Syndrome

Forty-nine patients with bilateral pigmentary dispersion syndrome (abnormal accumulation of pigment in the anterior chamber, principally from the posterior layers of the iris), including 31 patients with pigmentary glaucoma, underwent 10% phenylephrine testing in one eye for evaluation of liberation of pigment floaters into the anterior chamber and the influence of phenylephrine on the intraocular pressure. Ten patients with pigmentary glaucoma developed a 3+ to 4+ pigment response, but only two demonstrated a pressure rise greater than 2 mm Hg. The highest pressure rise observed was 7 mm Hg. Nine patients with pigmentary dispersion syndrome but without glaucoma also developed a 3+ to 4+ pigment response, but none of these had a pressure rise. The incidence of pigment liberation was higher in older patients and in pigmentary glaucoma patients receiving topical antiglaucoma therapy at the time of testing. The extent of iris transillumination did not correlate with the grade of phenylephrine-induced pigment liberation. Two pigmentary glaucoma patients, who did not liberate pigment or have a pressure rise when tested with phenylephrine, did exhibit spontaneous or exercise-induced liberations of pigment into the anterior chamber, with marked rises of intraocular pressure and obstruction of aqueous outflow.

Timolol in Uncontrolled Childhood Glaucomas

Thirty-four patients with childhood glaucoma who had difficult management problems in spite of conventional glaucoma medications were entered into an investigational protocol designed at a time when timolol was not available commercially. Since controlled studies in adult glaucoma had demonstrated the efficacy of timolol, a trial of the drug in these difficult childhood cases seemed justified. The study was approved by the Human Studies Committees of the Childrens Hospital Medical Center and the Massachusetts Eye and Ear Infirmary, Boston, MA. These children have been followed for periods up to 2 1/2 years. In general, timolol was added to the maximum tolerated medical therapy. Definite improvement was noted in 10 patients, modest or equivocal improvement in 11, and in 13 no substantial benefit to their course occurred when timolol was added. youngsters over 5 years of age showed an average reduction in resting pulse rate of 6 beats/minute similar to that previously found in adult patients. Under 5 years of age no change in the resting pulse rate could be detected. One patient was discontinued from timolol for a possible adverse effect. The experience particularly in very young children is still quite limited, but the beneficial effects observed warrant further evaluation.

Vitamin B12: correlation of serum concentrations and age.

Summary Total serum vit. B12 concentrations were determined in 528 individuals by the L. leichmannii method, and a justification for the choice of this method of assay is presented. The individuals studied were “normal” as far as physical health is concerned, and the major variable was age. In such persons there is a trend toward lower serum concentration of vit. B12 in the aged than in younger age groups. Although this difference is statistically significant, the biological importance of this finding is not apparent. There is wide individual difference of values in serum vit. B12 concentration at all age levels, but in this “normal” group values below 200 μμg/ml and above 1000 μμg/ml were uncommon. The average for the entire 528 individuals was 560 μμg/ml, the 95% confidence bands being 70 and 1060 μμg/ml respectively.

Biocytinase, an Enzyme Concerned with Hydrolytic Cleavage of Biocytin

Summary The existence in blood of an enzyme in relatively large amount, that accomplishes the hydrolysis of biocytin (∊-N-biotinyl-L-lysine) tentatively termed biocytinase has been pointed out. The enzyme has a pH optimum at 6.0-6.7 and requires for optimum effect the presence of an appropriate sulfhydryl compound.

Keratoconus and Acute Hydrops in Mentally Retarded Patients with Congenital Rubella Syndrome

Four patients with the congenital rubella syndrome had keratoconus and evidence of acute or previous corneal hydrops. All four of the patients vigorously rubbed and poked their eyes. The keratoconus and acute corneal hydrops in these patients probably resulted from chronic traumatizing mannerisms common in other patients with mental retardation and are not specific for the congenital rubella syndrome.

Late ocular complications in congenital rubella syndrome.

Ocular consequences of the congenital rubella syndrome are not limited to abnormalities noted in the neonatal period. Additional abnormalities may appear years and even decades after birth. Thirteen patients are presented in whom glaucoma has been diagnosed 3 to 22 years after birth. This acquired form of glaucoma has occurred in microphthalmic eyes in all but two cases. In all patients, the lens was cataractous early in life and had either been removed surgically or had been absorbed spontaneously. The diagnosis of late onset glaucoma appears to be difficult to make and is often overlooked. A smaller but overlapping group of patients with congenital rubella syndrome had keratic precipitates without other evidence of acute ocular inflammation. Recognition of these late ocular complications is particularly relevant, since the affected youngsters born during the last major US rubella epidemic in the early 1960s are now reaching late adolescence.

The Treatment of Glaucoma: Role of β-Blocking Agents

SummaryThe sudden development of a red painful eye with blurred vision may be an acute attack of angle closure glaucoma which requires emergency attention. Once the attack is controlled with medication, surgical intervention with a peripheral iridectomy is indicated to relieve relative pupillary block. Eyes subject to angle closure glaucoma are anatomically different with ‘crowded’ anterior segments.In contrast, open angle glaucoma (the more common form) may progress to near blindness without symptoms. Routine screening of intraocular pressure is, therefore, necessary to make the diagnosis before extensive irreparable damage has occurred. Surgery for open angle glaucoma carries risks of cataract and infection, and is unpredictable. Open angle glaucoma patients are usually treated chronically with specific medications. β-Adrenoceptor blocking agents appear to provide a significant new addition to the currently available antiglaucoma medications.