Mae O. Gordon

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.

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.

Controlled Trial of Transfusions for Silent Cerebral Infarcts in Sickle Cell Anemia

BACKGROUND Silent cerebral infarcts are the most common neurologic injury in children with sickle cell anemia and are associated with the recurrence of an infarct (stroke or silent cerebral infarct). We tested the hypothesis that the incidence of the recurrence of an infarct would be lower among children who underwent regular blood-transfusion therapy than among those who received standard care. METHODS In this randomized, single-blind clinical trial, we randomly assigned children with sickle cell anemia to receive regular blood transfusions (transfusion group) or standard care (observation group). Participants were between 5 and 15 years of age, with no history of stroke and with one or more silent cerebral infarcts on magnetic resonance imaging and a neurologic examination showing no abnormalities corresponding to these lesions. The primary end point was the recurrence of an infarct, defined as a stroke or a new or enlarged silent cerebral infarct. RESULTS A total of 196 children (mean age, 10 years) were randomly assigned to the observation or transfusion group and were followed for a median of 3 years. In the transfusion group, 6 of 99 children (6%) had an end-point event (1 had a stroke, and 5 had new or enlarged silent cerebral infarcts). In the observation group, 14 of 97 children (14%) had an end-point event (7 had strokes, and 7 had new or enlarged silent cerebral infarcts). The incidence of the primary end point in the transfusion and observation groups was 2.0 and 4.8 events, respectively, per 100 years at risk, corresponding to an incidence rate ratio of 0.41 (95% confidence interval, 0.12 to 0.99; P=0.04). CONCLUSIONS Regular blood-transfusion therapy significantly reduced the incidence of the recurrence of cerebral infarct in children with sickle cell anemia. (Funded by the National Institute of Neurological Disorders and Stroke and others; Silent Cerebral Infarct Multi-Center Clinical Trial ClinicalTrials.gov number, NCT00072761, and Current Controlled Trials number, ISRCTN52713285.).

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.

Biomicroscopic signs and disease severity in keratoconus

The Collaborative Longitudinal Evaluation of Keratoconus (CLEK) Survey represents the largest sample of clinic-based keratoconus patients to date. Data were collected at 38 clinical centers on 1,579 keratoconus patients. This article reports demographic variables, ages, self-reported ages at diagnosis, keratometry, slit-lamp findings, systemic disease, family history of keratoconus, and best spectacle-corrected and contact lens-corrected visual acuity of this sample group. The average age of this clinic-based sample group was 37 years (range 10-89 years), with 84% between 20 and 49 years old. Thirteen percent of patients had unilateral keratoconus, defined as unilateral corneal irregularity. More advanced disease (steeper average keratometric reading) was associated with a greater likelihood of Vogts striae, Fleischers ring, and/or corneal scarring. Fifty-eight percent of the eyes in this group of patients had ≥40/40 visual acuity with manifest refraction. Penetrating keratoplasty was reported in 12.3% of eyes. This prospective survey identifies the association between the presence of Vogts striae, Fleischers ring, and/or corneal scarring and increasing steepness, as measured by keratometry.

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.

Associated risk factors for silent cerebral infarcts in sickle cell anemia: low baseline hemoglobin, sex, and relative high systolic blood pressure

The most common form of neurologic injury in sickle cell anemia (SCA) is silent cerebral infarction (SCI). In the Silent Cerebral Infarct Multi-Center Clinical Trial, we sought to identify risk factors associated with SCI. In this cross-sectional study, we evaluated the clinical history and baseline laboratory values and performed magnetic resonance imaging of the brain in participants with SCA (HbSS or HbSβ° thalassemia) between the ages of 5 and 15 years with no history of overt stroke or seizures. Neuroradiology and neurology committees adjudicated the presence of SCI. SCIs were diagnosed in 30.8% (251 of 814) participants who completed all evaluations and had valid data on all prespecified demographic and clinical covariates. The mean age of the participants was 9.1 years, with 413 males (50.7%). In a multivariable logistic regression analysis, lower baseline hemoglobin concentration (P < .001), higher baseline systolic blood pressure (P = .018), and male sex (P = .030) were statistically significantly associated with an increased risk of an SCI. Hemoglobin concentration and systolic blood pressure are risk factors for SCI in children with SCA and may be therapeutic targets for decreasing the risk of SCI. This study is registered at www.clinicaltrials.gov as #NCT00072761.

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.

T cell subsets and sIL-2R/IL-2 levels in patients with glaucoma.

PURPOSE We hypothesize that cellular immunity may have a previously unrecognized role in glaucomatous optic neuropathy. The purpose of this study is to analyze subsets of T cells and the levels of cytokine IL-2 and the soluble IL-2 receptor in peripheral blood from patients with normal pressure glaucoma (NPG) or primary open angle glaucoma (POAG) in comparison to age-matched control subjects. METHODS In this study, 38 patients (20 NPG; 18 POAG) and 19 controls were included. sIL-2R and IL-2 were assayed by ELISA. T cell subsets were analyzed by flow cytometry and lymphocyte proliferation was used to measure the reactive ability of T cells to phytohemagglutinin (PHA). RESULTS The frequency of CD8(+)HLA-DR(+) lymphocytes were increased in patients with NPG (P = 0.008), and CD3(+)CD8(+) lymphocytes increased in both NPG (P = 0.03) and POAG patients (P = 0.0004). CD5(+) lymphocytes were higher only in POAG patients (P = 0.0012). In comparison to controls, the ratio of CD4(+)/CD8(+) lymphocytes was similar in both groups. The mean concentrations of sIL-2R in NPG (P = 0.011) and POAG (P = 0.0023) patients were higher than that found in control subjects although IL-2 concentrations were similar in these groups. In addition, the reactive ability of T lymphocytes to the non-specific reagent (PHA) was reduced significantly in NPG (P = 0.02) and POAG patients (P=0.04). CONCLUSION The alterations of the cellular immune system in patients with glaucoma support our hypothesis that the immune system may play an important role in the initiation and/or sustainment of glaucomatous optic neuropathy in some patients.

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.