Localization of a locus (GLC1B) for adult-onset primary open angle glaucoma to the 2cen-q13 region.

Primary open angle glaucoma (GLC1) is a common ocular disorder with a characteristic degeneration of the optic nerve and visual field defects that is often associated with an elevated intraocular pressure. The severe but rare juvenile-onset type has previously been mapped to 1q21-q31, and its genetic heterogeneity has been established. Herein, we present a new locus (GLC1B) for one form of GLC1 on chromosome 2cen-q13 with a clinical presentation of low to moderate intraocular pressure, onset in late 40s, and a good response to medical treatment. Two-point and haplotype analyses of affected and unaffected meioses in six families provided maximum linkage information with D2S417, GATA112EO3, D2S113, D2S373, and D2S274 (lod scores ranging from 3.11 to 6.48) within a region of 8.5 cM that is flanked by D2S2161 and D2S2264. Analysis of affected meioses alone revealed no recombination with an additional two markers (D2S2264 and D2S135) in a region of 11.2 cM that is flanked by D2S2161 and D2S176. Analysis of unaffected meioses identified only one healthy 86-year-old male who has inherited the entire affected haplotype and, hence, is a gene carrier for this condition. Eight additional families with similar and/or different clinical presentation did not show any linkage to this region and, therefore, provided evidence for genetic heterogeneity of adult-onset primary open angle glaucoma.

A comparison of the ocular hypotensive effect of 0.025% bromocriptine and 0.25% timolol eye drops in normal human volunteers.

1. The ocular hypotensive effect of 0.025% bromocriptine and 0.25% timolol eye drops was compared in nine healthy human volunteers, using non-contact tonometry. 2. Considering all post-dosing measurements compared with placebo and including the baseline values as continuous independent variables, using multiple linear regression analysis, both bromocriptine and timolol had a significant ocular hypotensive effect (P less than 0.0001) in the treated eye with a significant but lesser effect in the contralateral eye. 3. In the concentrations used, timolol was more efficacious than bromocriptine in lowering intraocular pressure (P less than 0.025). 4. Using other forms of vehicles for bromocriptine to improve efficacy and studying the ocular hypotensive effect of topical application of other dopamine-2-receptor agonists such as pergolide and lisuride was suggested.

Effects of adrenergic drugs on aqueous humour dynamics in the normal human eye. I. Salbutamol.

The immediate effects of topical salbutamol, a beta 2 adrenergic agonist, on the aqueous humour dynamics of 22 normal subjects was studied by fluorophotometry and tonography. Significant lowering of intraocular pressure was accompanied by a significant increase in both aqueous flow rate and tonographic facility of outflow. Uveoscleral outflow was calculated and found to be significantly increased by salbutamol. This appeared to be the predominant acute pressure lowering effect of beta receptor stimulation in the normal human eye.

Effects of long-term treatment with timolol on lacrimal gland function.

Thirty-two patients with raised intraocular pressure were treated for 1 year with topical timolol 0.5% twice daily. There was satisfactory pressure reduction on this drug alone in 25 patients. The tear flow (modified Schirmer I test) was measured, and the tear lysozyme concentration was assayed before, and at 3, 6, and 12 months after beginning treatment. No subjective symptoms occurred and no side effects were recorded. The tear flow and tear lysozyme concentration were not significantly reduced.

Quantitative tear lysozyme assay: a new technique for transporting specimens.

We have developed a method for assaying the concentration of tear lysozyme using eluates of tear fluid collected on filter paper discs. Specimens can be stored and transported to remote laboratories for assay. We have shown that the 'indirect' or eluate method gives statistically comparable results to the 'direct' method using fresh, neat tear fluid.

Binocular reflexes in the first 6 months of life: preliminary results of a study of normal infants.

The development of the binocular reflexes during the first 6 months of life was studied in 38 normal infants. Preliminary results indicate that the following reflex is well established by 2 months, convergence by 3 months and the corrective fusion reflex by the age of 5 months.

Anterior chamber volume. Its measurement and clinical application.

Measurement of anterior chamber volume is discussed and attention drawn to a new, convenient slit-image method, which was used to study anterior chamber depth and volume before and after prophylactic peripheral iridectomy in the fellow eyes of patients presenting with unilateral acute angle-closure glaucoma. There was no significant change in depth after iridectomy but the mean anterior chamber volume increased significantly (P less than 0.01), by nearly 3 per cent. This increase was due to elimination of peripheral iris bombé which was not present in two control groups of normal eyes, one matched for anterior chamber depth and the other for age and refraction. Peripheral iris bombé may be a quantifiable factor predisposing to the development of acute angle-closure glaucoma.

Method of measuring aqueous humor flow and corneal endothelial permeability using a fluorophotometry nomogram.

A new method of measuring aqueous humor flow and corneal endothelial permeability to fluorescein using a fluorophotometry nomogram is described. This method is compared to four other methods, two of which have been described previously. All five methods were carried out simultaneously in a group of 20 normal human subjects. All methods give closely comparable results in most of the eyes tested. A tabular comparison of the results of the nomographic method and the published results of other investigators, which are in good agreement, is given. The relative advantages and disadvantages of the nomographic technique are discussed.

Effect of timolol on the permeability of corneal endothelium.

The effect of short-term administration of timolol on the permeability of the corneal endothelium to fluorescein was measured in normal subjects (single drop) and in a small group of glaucoma patients (one week's treatment). No effect on the endothelium was found in the normal eyes. In the glaucomatous eyes, endothelial permeability was higher than normal when measured after one week without topical medications and normal when measured after one week on timolol treatment. No evidence was found that short-term administration of this drug disturbs the barrier function of the endothelium.

The mechanism of timolol in lowering intraocular pressure. In the normal eye.

A single-drop, double-masked, randomized, placebo-controlled study of the mechanism of the ocular-pressure lowering property of timolol maleate, a beta-adrenergic blocker, was carried out in 23 normal subjects, using fluorophotometry. Timolol suppressed aqueous formation in all subjects. The range of suppression was 13% to 48%, with a mean +/- SD of 34% +/- 9%. The drug had no effect on anterior chamber volume or endothelial permeability to fluorescein and, apparently, had no effect on outflow resistance. No differences were observed between its effect on men and women or between eyes with light and dark irides.

Use of a xenon flash tube as the excitation source in a new slit-lamp fluorophotometer.

A new objective fluorophotometer measures fluorescein mass or concentration in the cornea or anterior chamber. The excitation source is a xenon flash tube that allows the measurement of fluorescence to be made rapidly and conveniently. The instrument is designed for use in clinical studies requiring quantitative measurements of fluorescence in the tears, the cornea, and the aqueous humor.

A simple photogrammetric method of measuring anterior chamber volume.

We devised a convenient method of measuring anterior chamber volume in man. Photographs of the anterior chamber were taken with a Zeiss photographic slit lamp with a Polaroid attachment, and measured with a specially constructed transparent scale. Using this method, the standard deviation of individual measurements of volume on different occasions in a given eye was 8 microliter. The standard deviation of the differences between right and left eyes of normal subjects was 10 microliter. The volume of the anterior chamber measured in 78 eyes of 39 normal subjects (mean age, 28 years; range, 19 to 56 years) was found to be 209 +/- 37 microliter (mean +/- SD). We observed a small negative correlation between the age of the subject and the volume of the anterior chamber.

Long-term follow-up of patients after retinal detachment surgery.

The value of long-term follow-up of patients after retinal detachment surgery depends on the number of further detachments prevented. This in turn depends on the frequency with which predisposing lesions are found and treated and also the risk of leaving them untreated. In a retrospective study of 128 patients who had attended the Retina Clinic at Moorfields, High Holborn, for at least 10 years, the frequency with which asymptomatic retinal breaks were detected was less than two per hundred patients per year of follow-up. The risk of such lesions progressing to detachment if left untreated is estimated to be no more than 12 per cent and on this basis it is likely that no more than four or five detachments were prevented in our series. During the same period 66 new or re-detachments occurred, in spite of regular examination and treatment of predisposing lesions found, and it is concluded that long-term follow-up is of doubtful value in the prevention of further detachments.