Michael A. Kass

Central corneal thickness in the ocular hypertension treatment study (OHTS)

OBJECTIVE Central corneal thickness influences intraocular pressure (IOP) measurement. We examined the central corneal thickness of subjects in the Ocular Hypertension Treatment Study (OHTS) and determined if central corneal thickness is related to race. DESIGN Cross-sectional study. PARTICIPANTS One thousand three hundred one OHTS subjects with central corneal thickness measurements. INTERVENTION Central corneal thickness was determined with ultrasonic pachymeters of the same make and model at all clinical sites of the OHTS. MAIN OUTCOME MEASURES Correlation of mean central corneal thickness with race, baseline IOP, refraction, age, gender, systemic hypertension, and diabetes. RESULTS Mean central corneal thickness was 573.0 +/- 39.0 microm. Twenty-four percent of the OHTS subjects had central corneal thickness > 600 microm. Mean central corneal thickness for African American subjects (555.7 +/- 40.0 microm; n = 318) was 23 microm thinner than for white subjects (579.0 +/- 37.0 microm; P < 0.0001). Other factors associated with greater mean central corneal thickness were younger age, female gender, and diabetes. CONCLUSIONS OHTS subjects have thicker corneas than the general population. African American subjects have thinner corneas than white subjects in the study. The effect of central corneal thickness may influence the accuracy of applanation tonometry in the diagnosis, screening, and management of patients with glaucoma and ocular hypertension.

The ocular hypertension treatment study.

Methods: One thousand six hundred thirty-six individuals with intraocular pressure (IOP) from 24 to 32 mm Hg in 1 eye and 21 to 32 mm Hg in the fellow eye were randomized to observation or to topical ocular hypotensive medication. Median time of treatment in the medication group was 13.0 years. After a median of 7.5 years without treatment, the observation group received medication for a median of 5.5 years. To determine if there is a penalty for delaying treatment, we compared the cumulative proportions of participants who developed POAG at a median follow-up of 13 years in the original observation group and in the original medication group.

Compliance with Topical Pilocarpine Treatment

Using an unobtrusive eyedrop medication monitor, we measured compliance with topical pilocarpine treatment in a sample of 184 patients. The eyedrop monitor recorded electronically the date and time of each pilocarpine administration over a four- to six-week period. The subjects administered a mean +/- S.D. of 76.0% +/- 24.3% of the prescribed pilocarpine doses. Eleven patients (6%) took less than one quarter and 28 patients (15.2%) took less than one half of the prescribed administrations. In contrast, when the subjects were interviewed they reported taking a mean +/- S.D. of 97.1% +/- 5.9% of the prescribed pilocarpine doses. As determined by the monitor, 45 patients (24.5%) had at least one day per month with no administrations of pilocarpine; 56 subjects (30.4%) compressed the doses during the daytime hours, leaving an interval between the night dose and the morning dose the next day of 12 hours or more. The rate of compliance was significantly higher (P less than .0001) in the 24-hour period preceding the return appointment than in the entire observation period.

Compliance With Topical Timolol Treatment

To determine if compliance with timolol treatment was better than compliance with pilocarpine treatment (as reported previously), we measured compliance with timolol treatment in a sample of 110 patients using an unobtrusive eyedrop medication monitor, which recorded electronically the date and time of each drug administration over a four- to six-week period. The patients administered a mean +/- S.D. of 82.7% +/- 19.0% of the prescribed timolol doses (range, 20% to 100%). Forty-five patients were treated concurrently with timolol and pilocarpine. These patients administered a mean +/- S.D. of 84.3% +/- 14.0% of the prescribed timolol doses and 77.7% +/- 18.7% of the prescribed pilocarpine doses (P = .012, van der Waerden test). Our results suggest that while compliance is influenced by the drug regimen, defaulting is not eliminated by prescribing a more convenient medication with fewer side effects.

Plasma and Aqueous Humor Endothelin Levels in Primary Open-Angle Glaucoma

Purpose:Endothelins (ET) have some effects on the regulation of aqueous humor dynamics. To investigate their possible role in glaucoma, we measured plasma and aqueous humor ET levels in patients with and without primary open-angle glaucoma. Methods:Plasma and aqueous humor samples were obtained from 31 patients with primary open-angle glaucoma and 24 patients without glaucoma. Measurements were made by radioimmunoassay (RIA) for ETs with the following crossreactivities: ET-1, ET-2, and big ET-1, 100%; and ET-3, 70%. Results:The ages (mean ± SD) of the patients with primary open-angle glaucoma (72.3 ± 10 years) and normal subjects (72.8 ± 8 years) were similar (p = 0.92). There was no significant difference between plasma ET levels of the two groups (p = 0.07). However, aqueous humor ET levels (mean ± SD) were higher in the primary open-angle glaucoma group (44.26 ± 2.6 pg ml-1) than in normal subjects (42.17 ± 1.6 pg ml-1) (p = 0.001). The ratios of corresponding aqueous humor to plasma levels of ETs were ∼10% higher in the primary open-angle glaucoma group (3.76) than in normal subjects (3.41) (p = 0.0002). Conclusions:The small increase in aqueous humor endothelin levels in patients with primary open-angle glaucoma versus controls of similar age may be relevant to the understanding of the various roles of ETs in aqueous humor dynamics in these patients.

Systemic factors in patients with low-tension glaucoma.

Nineteen patients (38 eyes) with low-tension glaucoma were compared with 53 subjects (106 eyes) with ocular hypertension. Comparable for age and sex, the 2 groups were assessed with respect to haematological and biochemical criteria, physical activity, and medical history. Statistical analyses of the differences between the 2 groups highlighted the importance of diastolic ophthalmodynamometry levels, prediagnosis exercise habits, cardiovascular disease status, and possibly systolic blood pressure. Patients with low-tension glaucoma suffered a higher prevalence of multiple abnormalities of these systemic factors than did their ocular hypertensive counterparts. There were no significant differences between the 2 groups with respect to the many other factors examined.

Can Ophthalmologists Correctly Identify Patients Defaulting from Pilocarpine Therapy

We determined whether clinical measurements and assessments available to ophthalmologists could be used to identify patients who default from pilocarpine treatment. The measurements and assessments included intraocular pressure, pupillary diameter, pupillary reactivity to light, the patients report of compliance, the physicians prediction of compliance, the patients log of pilocarpine administration, and the weight of pilocarpine eyedrops utilized. Compliance with the pilocarpine regimen was measured with an unobtrusive eyedrop medication monitor. Intraocular pressure and pupillary diameter did not correlate with compliance to the regimen as measured by the eyedrop monitor. Pupillary reaction to light, the physicians prediction of compliance, a daily log of pilocarpine administration, the weight of pilocarpine utilized, and the patients report of compliance correlated modestly with compliance as measured by the monitor (range of correlations, 0.19 to 0.24). However, none of these measures taken by itself or combined in any manner adequately distinguished patients with lower rates of compliance from those with higher rates of compliance. At present, the eyedrop monitor is the only reliable method for detecting patients who default from treatment.

Follow-up of Angle-closure Glaucoma Suspects

One hundred twenty-nine patients thought to be at risk for developing angle-closure glaucoma underwent a baseline examination, which included gonioscopy, refraction, anterior chamber pachymetry, ultrasound biometry, and an angle-closure provocative test. Patients were then followed up with no treatment. Mean follow-up was 2.7 years with a range up to six years. Twenty-five patients developed angle closure in at least one eye during the follow-up period, but in most (17 of the 25 patients), the angle closure was nonacute (that is, no clinical signs or symptoms and no increase in intraocular pressure). None of the test factors studied showed a high sensitivity or positive predictive accuracy in detecting the eyes that later developed angle closure.

Delaying Treatment of Ocular Hypertension The Ocular Hypertension Treatment Study

OBJECTIVE To compare the safety and efficacy of earlier vs later treatment in preventing primary open-angle glaucoma (POAG) in individuals with ocular hypertension. METHODS One thousand six hundred thirty-six individuals with intraocular pressure (IOP) from 24 to 32 mm Hg in 1 eye and 21 to 32 mm Hg in the fellow eye were randomized to observation or to topical ocular hypotensive medication. Median time of treatment in the medication group was 13.0 years. After a median of 7.5 years without treatment, the observation group received medication for a median of 5.5 years. To determine if there is a penalty for delaying treatment, we compared the cumulative proportions of participants who developed POAG at a median follow-up of 13 years in the original observation group and in the original medication group. MAIN OUTCOME MEASURES Cumulative proportion of participants who developed POAG. RESULTS The cumulative proportion of participants in the original observation group who developed POAG at 13 years was 0.22 (95% confidence interval [CI], 0.19-0.25), vs 0.16 (95% CI, 0.13-0.19) in the original medication group (P = .009). Among participants at the highest third of baseline risk of developing POAG, the cumulative proportion who developed POAG was 0.40 (95% CI, 0.33-0.46) in the original observation group and 0.28 (95% CI, 0.22-0.34) in the original medication group. There was little evidence of increased adverse events associated with medication. APPLICATION TO CLINICAL PRACTICE Absolute reduction was greatest among participants at the highest baseline risk of developing POAG. Individuals at high risk of developing POAG may benefit from more frequent examinations and early preventive treatment. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00000125.

Intraocular Pressure Response to Topical Dexamethasone as a Predictor for the Development of Primary Open-Angle Glaucoma

In a retrospective study we reviewed the records of 788 subjects who had been corticosteroid tested with 0.1% dexamethasone four times daily to one eye for six weeks. All subjects had normal kinetic visual fields and optic nerve heads in both eyes at the time of testing and were followed up for a minimum of five years. Some subjects had normal baseline intraocular pressures whereas others were considered to have ocular hypertension. Of 276 individuals who were high corticosteroid responders (intraocular pressure greater than 31 mm Hg during dexamethasone administration), 36 (13.0%) developed glaucomatous visual field loss during the follow-up period. Only nine of 261 individuals (3.4%) who were intermediate responders (intraocular pressure 20 to 31 mm Hg during dexamethasone administration) and none of 251 individuals who were low responders (intraocular pressure less than 20 mm Hg during dexamethasone administration) developed glaucomatous visual field loss. However, the ability of the intraocular pressure response to dexamethasone to predict the development of glaucomatous visual field loss was not as good as the predictive power of a multivariate model that included patient age, race, baseline intraocular pressure, baseline outflow facility, baseline cup/disk ratio, and systemic hypertension.