Jacqueline S. Lustgarten

Maintained reduction of intraocular pressure by prostaglandin F2α-1-isopropyl ester applied in multiple doses in ocular hypertensive and glaucoma patients

In a randomized, double-masked, placebo-controlled study, 0.25 microgram (n = 11) or 0.5 microgram (n = 13) of prostaglandin F2 alpha-1-isopropyl ester (PGF2 alpha-IE) was applied topically twice daily for 8 days to one eye of ocular hypertensive or chronic open-angle glaucoma patients. Compared with contralateral, vehicle-treated eyes, PGF2 alpha-IE significantly (P less than 0.05) reduced intraocular pressure (IOP), beginning 4 hours after the first 0.5-microgram dose and lasting at least 12 hours after the fourteenth dose, with a significant (P less than 0.005) mean reduction of 4 to 6 mmHg maintained throughout the last day of therapy with either dose. A contralateral effect was not observed. Mean tonographic outflow facility was significantly (P less than 0.05) higher in PG-treated compared with vehicle-treated eyes (0.17 +/- 0.02 versus 0.12 +/- 0.01 microliter/minute/mmHg, respectively; +/- standard error of the mean) for the 0.5 microgram dose. Conjunctival hyperemia reached a maximum at 30 to 60 minutes after PGF2 alpha-IE application. Some patients reported mild irritation lasting several minutes after some doses. Visual acuity, accommodative amplitude, pupillary diameter, aqueous humor flare, anterior chamber cellular response, Schirmers test, pulse rate, and blood pressure were not significantly altered. Our findings show that PGF2 alpha-IE is a potent ocular hypotensive agent and a promising drug for glaucoma therapy.

Electrophysiological evidence that early glaucoma affects foveal vision

The pattern electroretinogram (PERG) and visual evoked potential (PVEP) were recorded simultaneously using a 1.1 cpd pattern which was counterphase modulated at 1 Hz. The responses of ocular hypertensive (OHT) eyes (with normal visual fields) and eyes with early glaucoma (with early visual field defects and/or early cupping of the optic nervehead) were compared to age-matched normal observers. All patients (26 eyes) and normal observers (14 eyes) had normal transient flash electroretinograms. Delays were seen in mean PERG latency in both OHT and early glaucoma eyes, while mean PERG amplitude was significantly reduced only in the early glaucoma eyes. The PVEP responses were ‘unmeasurable’ in 11/26 patient eyes because the waveforms were grossly abnormal in shape, making it impossible to identify the N- and P-components. The data were categorized in this manner: a patient response was considered abnormal if latency or amplitude exceeded normal limits (PERG or PVEP) or if the waveform was ‘unmeasurable’ due to its shape (PVEP only). Of the 26 patient eyes, we found that 8 eyes had normal PERG and PVEP, 11 eyes had abnormal PERG and PVEP, one eye had an abnormal PERG and a normal PVEP, and 6 eyes (3 patients) had a normal PERG and an abnormal PVEP. These data support the proposition that foveal vision (as assessed by the PVEP) may be affected by early glaucomatous damage. The relationship between the PERG and PVEP also was evaluated using a new measurement which we call the ‘latency window’. Using this measurement, 15/26 patient eyes were abnormal - 9 of these had ‘unmeasurable’ PVEPs. This measurement could be useful in classifying ‘W’-shaped PVEPs as normal or abnormal.

Long-Term Reduction of Intraocular Pressure After Repeat Argon Laser Trabeculoplasty

Thirty-eight eyes (in 31 patients with glaucoma) that had shown a favorable response to an initial argon laser trabeculoplasty had a repeat laser trabeculoplasty four to 81 months (mean +/- S.E.M., 23 +/- 3 months) later because of inadequately controlled intraocular pressures. A mean (+/- S.E.M.) of 65 +/- 3 burns (range, 50 to 115) were given during the initial laser trabeculoplasty, and 58 +/- 2 burns (range, 36 to 100) were given during the first repeat treatment. Three months after the first repeat laser trabeculoplasty, one eye (3%) had undergone filtering surgery and 30 eyes (78%) were considered successes. Of the 30 eyes that were followed up for 12 months after the first repeat laser trabeculoplasty, two (7%) had undergone filtering surgery, three (10%) had received a second repeat laser trabeculoplasty, and 22 (73%) were successes. Fifteen eyes underwent a second repeat laser trabeculoplasty at six to 47 months (mean +/- S.E.M., 21 +/- 3 months) after the first repeat laser trabeculoplasty. Seven (47%) of these eyes required filtering surgery within three to 12 months after the second repeat laser trabeculoplasty. Four of 38 (11%) of the initial, two of 38 (5%) of the first repeat, and zero of 15 of the second repeat laser trabeculoplasty treatments resulted in a one- to two-hour rise in intraocular pressure of at least 10 mm Hg.

A Clinical Trial of Metipranolol, a Noncardioselective Beta-Adrenergic Antagonist, in Ocular Hypertension

In randomized, double-masked fashion, 24 volunteers with ocular hypertension received 0.3% or 0.6% metipranolol, a noncardioselective beta blocker; or placebo twice daily to both eyes for six weeks. Intraocular pressure (mean +/- SEM) was reduced (P = .01) in the metipranolol-treated patients (baseline measurement, 25.9 +/- 0.5 mm Hg to 18.1 +/- 1.2 mm Hg at six weeks, 0.6% concentration; baseline measurement, 27.1 +/- 0.4 mm Hg to 21.6 +/- 1.5 mm Hg at six weeks, 0.3% concentration). Intraocular pressure was not markedly changed in placebo-treated patients. Outflow facility was unaltered two hours after instillation of metipranolol at study week 2 compared to baseline measurement. Aqueous humor flow rates were reduced (P = .02) 20% after 0.6% or 0.3% metipranolol instillation and were unchanged after placebo administration compared to baseline measurement. Mean systolic blood pressure, diastolic blood pressure, and pulse rate were not markedly altered. Metipranolol reduces intraocular pressure by suppressing aqueous humor flow rates.

The effect of corynanthine on intraocular pressure in clinical trials.

A single drop, dose-response, double-masked study of the effect corynanthine, a selective alpha 1 adrenergic antagonist, on intraocular pressure (IOP) was carried out in 10 symmetrically ocular hypertensive patients. Corynanthine 1% had no significant pressure lowering effect. Topical application of a 2% solution significantly (P less than 0.05) reduced IOP for at least eight hours; at five hours, mean IOP (+/- SEM) was 20.6 +/- 2.0 mmHg and 26.0 +/- 4.9 mmHg, comparing treated and control eyes, respectively. The 5% solution caused a significant (P less than 0.05) bilateral reduction in IOP, comparing treated and control eyes to baseline IOP respectively. Two percent corynanthine applied topically two or three times daily for one, two, or three weeks to seven patients with symmetrical ocular hypertension did not reduce IOP. Alpha adrenergic antagonists may have a role in the treatment of glaucoma.

Comparison of Standard and Computerized Tonography Instruments on Human Eyes

We compared the outflow facility coefficient results after indentation tonography obtained with a standard tonography unit and with a new computerized tonography machine. Goldmann applanation tonometry was followed by standard tonography on one eye and computerized tonography on the other. After a one-hour equilibration period, tonometry was repeated and followed by tonography with the testing units used on the opposite eyes. In nine of 60 eyes the results were discarded because of poor tracings or high error. Results of initial indentation intraocular pressure measured by the two units were not statistically different from those measured by Goldmann applanation tonometry. Mean outflow facilities determined by the standard unit and by the computerized machine with the average scleral rigidity program showed no statistically significant difference by the paired t-test.

Influence of treatment protocol on the long-term efficacy of argon laser trabeculoplasty.

Forty-five phakic eyes of 36 patients with open-angle glaucoma and uncontrolled intraocular pressure despite maximally tolerated medication underwent initial argon laser trabeculoplasty (ALT) in 1981 and 1982 as part of a prospective, randomized study to evaluate the effectiveness of different treatment standards. Each eye had been randomly assigned to receive either 100 laser applications over 360 degrees of trabecular meshwork, 50 applications over 180 degrees , or 50 applications over 360 degrees in a single session. Further treatment in each group was based on clinical standards prevailing at the time. The long-term results were analyzed using Kaplan-Meier survival analyses. By 4 years after initial ALT, six of the 15 remaining eyes in group 1 (40%), one of 14 eyes in group 2 (7%), and two of 13 eyes in group 3 (15%) had undergone filtration surgery, and one eye in group 1 (7%), three eyes in group 2 (21%), and three eyes in group 3 (23%) had received further ALT. By 7 years after initial ALT, seven of the nine remaining eyes in group 1 (78%), one of 12 eyes in group 2 (8%), and four of 12 eyes in group 3 (33%) received filtration surgery, and two eyes in group 1 (22%), three eyes in group 2 (25%), and four eyes in group 3 (33%) had received further ALT. Kaplan-Meier survival curves predict the following probabilities of avoiding either repeat ALT or filtration surgery at 4 years after an initial ALT: group 1, 54 +/- 12%; group 2, 76 +/- 12%; and group 3, 62 +/- 11%. Our results suggest that performing 50 rather than 100 burns at initial ALT may significantly delay the need for additional surgical or repeat laser intervention.

Segmental analysis of computerized optic nerve head imaging.

We evaluated a new method of segmental analysis of the array of numbers representing the depths at points on the optic nerve as generated by a computerized retinal topographic imaging system (the Humphrey Retinal Analyzer). We divided the observed optic nerve head into five rectangular areas, determined the mean depth of each of these areas, and compared them statistically. Intraobserver, interimage, and interobserver variability were calculated. The range of intraobserver variability (+/-SEM) was +/-1.2 to +/-12.0 mum, median 4.6 mum. Interimage variability ranged from +/-3.0 to +/-30.8 mum, median 14.7 mum. Interobserver variability, assessed by intraclass correlation coefficient and two-way analysis of variance, showed observer-to-observer variability was not significant as compared to subject variance and subject-observer interaction variance. Clinical studies further evaluating this segmental analysis of computerized data from the Heidelberg Retinal Tomograph are in progress.