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.

Corneal scarring and vision in keratoconus: a baseline report from the Collaborative Longitudinal Evaluation of Keratoconus (CLEK) Study.

PURPOSE: The multicenter Collaborative Longitudinal Evaluation of Keratoconus (CLEK) Study is a prospective, observational study of 1,209 keratoconus patients. We report on the correlation of corneal scarring with clinical and patient-reported variables at the baseline visit. METHODS: Patients completed a questionnaire on their vision, effect of glare, contact lens wear, and work-related issues. Clinical examination included high- and low-contrast visual acuity, refraction, assessment of corneal scarring by the clinician and by photography, and measurement of corneal curvature. The correlation of central corneal scarring with visual acuity and patient-reported variables was analyzed using multiple regression analysis and generalized estimating equations. RESULTS: High- and low-contrast visual acuity with habitual and optimal correction is reduced in scarred eyes. Multiple regression analyses controlling for age, contact lens wear, and disease severity show that central scarring is associated with poorer visual acuity and increased patient-reported symptoms of glare. Restrictions on day-to-day activities do not appear to be associated with corneal scarring above and beyond the effects of keratoconus alone. CONCLUSIONS: Corneal scarring in keratoconus is significantly associated with decreased high- and low-contrast visual acuity.

Contralateral effect of topical beta-adrenergic antagonists in initial one-eyed trials in the ocular hypertension treatment study.

PURPOSE: To evaluate the magnitude of the contralateral effect of topically administered beta-blockers on intraocular pressure. METHODS: The Ocular Hypertension Treatment Study enrolled 1,636 subjects. Of these, 817 subjects were randomized to receive topical ocular hypotensive medication and 819 subjects were randomized to close observation (i.e., no topical medication). We compared the intraocular pressure of the contralateral eye of subjects at the baseline visit and after an initial one-eyed therapeutic trial of topical beta-blockers. We examined differences between baseline and follow-up intraocular pressure in untreated eyes of subjects randomized to close observation. RESULTS: The mean reduction in intraocular pressure in the beta-blocker-treated eyes was -5.9 +/- 3. 4 mm Hg (-22% +/- 12%; Student t test, P <.0001). In the contralateral eyes, mean intraocular pressure reduction was -1.5 +/- 3.0 mm Hg (-5.8% +/- 12%; P <.0001). Of the contralateral eyes, 35% showed a reduction of 3 mm Hg or more, and 10% showed a reduction of 6 mm Hg or more. The contralateral effect of the relatively selective beta-blocker betaxolol did not differ from that of any of the nonselective beta-blockers. Factors associated with the magnitude of the contralateral effect were the degree of intraocular pressure reduction in the treated eye and baseline intraocular pressure of the contralateral eye. In the close observation group, no significant reduction in intraocular pressure was noted between the baseline and follow-up visit. CONCLUSIONS: The contralateral effect is important in clinical practice and in clinical trials when the hypotensive effect of a topical beta-blocker is evaluated by means of a one-eyed therapeutic trial.

Confirmation of visual field abnormalities in the Ocular Hypertension Treatment Study. Ocular Hypertension Treatment Study Group.

OBJECTIVE: To determine the frequency with which visual field abnormalities observed on follow-up visual fields for patients in the Ocular Hypertension Treatment Study were confirmed on retest. METHODS: Between April 1, 1994, and March 1, 1999, 21,603 visual fields were obtained from 1637 patients in the Ocular Hypertension Treatment Study. When follow-up visual fields are outside the normal limits on the Glaucoma Hemifield Test, the Corrected Pattern Standard Deviation (P<.05), or both, subsequent follow-up visual fields are monitored to confirm the abnormality. Abnormalities are confirmed if they are again abnormal on the Glaucoma Hemifield Test, the Corrected Pattern Standard Deviation, or both; if the defect is not artifactual; and if the same index and location are involved. Reliability criteria used by the study consisted of a limit of 33% for false positives, false negatives, and fixation losses. RESULTS: Of the 21,603 regular follow-up visual fields, 1006 were follow-up retests performed because of an abnormality (n = 748) or unreliability (n = 258). We found that 703 (94%) of the 748 visual fields were abnormal and reliable, and 45 (6%) were abnormal and unreliable. On retesting, abnormalities were not confirmed for 604 (85.9%) of the 703 originally abnormal and reliable visual fields. CONCLUSIONS: Most visual field abnormalities in patients in the Ocular Hypertension Treatment Study were not verified on retest. Confirmation of visual field abnormalities is essential for distinguishing reproducible visual field loss from long-term variability. Arch Ophthalmol. 2000;118:1187-1194

Factors associated with corneal scarring in the Collaborative Longitudinal Evaluation of Keratoconus (CLEK) Study.

PURPOSE: The multicenter Collaborative Longitudinal Evaluation of Keratoconus (CLEK) Study is a prospective, observational study of 1,209 keratoconus patients. We report on the factors associated with corneal scarring at baseline. METHODS: We defined corneal scarring as scars that had been detected both by the clinician examining the patient with the slit-lamp biomicroscope and by masked readers of corneal photographs at the CLEK Photography Reading Center. We investigated associations between corneal scarring and patient variables including gender, ethnicity, a family history of keratoconus, a history of ocular trauma, eye rubbing, contact lens wear, rigid contact lens fitting relationships, and corneal findings (such as curvature, Vogt's striae, Fleischer's ring, and central/apical staining). Multiple logistic regression analysis using generalized estimating equations to adjust for the correlation between eyes was used for analysis. RESULTS: The following factors were found to increase the odds of corneal scarring at baseline in the CLEK Study: corneal staining (odds ratios (OR) = 3.40, 95% confidence interval 2.53-4.59), contact lens wear (OR = 3.51, 95% confidence interval 2.27-5.45), Fleischer's ring (OR = 1.63, 95% confidence interval 1.11-2.40), steeper first definite apical clearance lens base curve radius (per diopter, OR = 1.29, 95% confidence interval 1.25-1.33), and age (per decade, OR = 1.54, 95% confidence interval 1.35-1.75). CONCLUSIONS: These baseline data suggest that corneal scarring in keratoconus is associated with corneal staining, contact lens wear, Fleischer's ring, a steeper cornea, and increasing age. The factors that imply added risk for corneal scarring that may be affected by practitioner intervention are staining of the cornea, contact lens wear, and the contact lens fitting relationship.

Rigid contact lens fitting relationships in keratoconus. Collaborative Longitudinal Evaluation of Keratoconus (CLEK) Study Group.

PURPOSE: Although the influence of flat-fitting contact lenses on corneal scarring in keratoconus is frequently debated, the current standard of care with regard to the apical fitting relationship in keratoconus remains undocumented. METHODS: Patients were examined at baseline in the Collaborative Longitudinal Evaluation of Keratoconus (CLEK) Study (N = 1209). Patients wearing a rigid contact lens in one or both eyes (N = 808) had their habitual rigid contact lenses analyzed, and the fluorescein patterns and base curves were compared to the first definite apical clearance lens (FDACL). The FDACL is the flattest lens in the CLEK Study trial lens set that exhibits an apical clearance fluorescein pattern. For patients wearing a rigid contact lens in both eyes, one eye was selected randomly for analysis. RESULTS: Twelve percent of the rigid contact lens-wearing eyes were wearing lenses fitted with apical clearance based upon the clinician's fluorescein pattern interpretation. The remainder (88%) was wearing lenses fitted with apical touch. For mild (steep keratometric reading <45 D) keratoconus corneas, the mean estimate of the base curve to cornea-fitting relationship was 1.18 D flat (SD +/- 1.84 D); moderate (steep keratometric reading: 45 to 52 D) corneas were fitted on average 2.38 D flat (SD +/- 2.56 D); and severe (steep keratometric reading > 52 D) corneas were fitted an average of 4.01 D flat (SD +/- 4.11 D). CONCLUSIONS: Despite the potential risk for corneal scarring imposed by flat-fitting rigid contact lenses, most CLEK Study patients wear flat-fitting lenses. Overall, rigid lenses were fitted an average of 2.86 D (SD +/- 3.31 D) flatter than the FDACL.

The Ocular Hypertension Treatment Study: design and baseline description of the participants.

BACKGROUND: The Ocular Hypertension Treatment Study (OHTS) seeks to evaluate the safety and efficacy of topical ocular hypotensive medication in preventing or delaying the onset of visual field loss and/or optic nerve damage in subjects with ocular hypertension at moderate risk for developing primary open angle glaucoma. OBJECTIVE: To describe the study protocol, the questions to be answered, and the baseline characteristics of the subjects. DESIGN: Multicenter randomized clinical trial with 2 groups: topical ocular hypotensive medication and close observation. SETTING: Subjects were enrolled and evaluated at 22 participating clinical centers. Visual fields and stereoscopic optic disc photographs were read in masked fashion. METHODS: We determined eligibility from a comprehensive eye examination, medical and ocular history, visual field testing, and stereoscopic optic disc photography. RESULTS: We describe the baseline characteristics of 1637 subjects randomized between February 28, 1994, and October 31, 1996. The mean age was 55 years; 56.9% of the subjects were women; and 25% were African American. The baseline intraocular pressure was 24.9 +/- 2.7 mm Hg (mean +/- SD). Systemic diseases and conditions reported by subjects included previous use of medication for ocular hypertension, 37%; systemic hypertension, 38%; cardiovascular disease, 6%; diabetes mellitus, 12%; and family history of glaucoma, 44%. The mean horizontal cup-disc ratio by contour estimated from stereophotography was 0.36 +/- 0.18. Qualifying Humphrey 30-2 visual fields had to be normal and reliable for entry into the study. Health-related quality of life (36-item short form health survey) scores in the OHTS sample were better than the age- and sex-matched population norms. African American subjects had larger baseline cup-disc ratios and higher reported rates of elevated blood pressure and diabetes than the rest of the subjects. CONCLUSIONS: The intraocular pressure among enrolled subjects was sufficiently high to provide an adequate test of the potential benefit of ocular hypotensive medication in preventing or delaying glaucomatous damage. The large number of African American subjects enrolled should provide a good estimate of the African American response to topical medication.

Corneal scarring in the Collaborative Longitudinal Evaluation of Keratoconus (CLEK) Study: baseline prevalence and repeatability of detection.

PURPOSE: The multicenter Collaborative Longitudinal Evaluation of Keratoconus (CLEK) Study is a prospective, observational study of 1,209 keratoconus patients. We report on the prevalence of corneal scarring in these patients. We also report on the test-retest repeatability of corneal scar documentation at the slit-lamp biomicroscope by trained clinicians and by masked photograph readers and on the scarring-status agreement at baseline between clinicians and photograph readers. METHODS: Clinicians and masked photograph readers graded each cornea as to scarring status. Patients were examined by clinicians, and their corneas were photographed at baseline (2,297 nongrafted eyes of 1,209 patients) and at a repeated visit (258 nongrafted eyes of 138 patients). These photographs were evaluated by the masked readers at the CLEK Photography Reading Center (CPRC). Clinicians reported corneal scars in right eyes at baseline as "definitely not present" in 53.9%, "probably not present" in 8.4%, "probably present" in 8.2%, and "definitely present" in 29.4% of patients. A weighted kappa statistic of 0.83 (95% confidence interval from 0.78 to 0.88) indicates that agreement is excellent between baseline and repeated assessments for the presence of a corneal scar by clinicians. RESULTS: Agreement is very good between baseline and repeated photograph-reader assessments for the presence of a scar, with a weighted kappa of 0.77 (95% confidence interval, 0.72-0.82). The kappa statistic comparing photograph-reader scarring assessments with clinician results was 0.69 (95% confidence interval, 0.66-0.71). CONCLUSION: The data also suggest better agreement between clinicians and readers when Vogt's striae and corneal nerves were observed. The data also suggest better agreement when corneal staining was not observed by the photograph readers. The CLEK Study protocol for determining the presence of scars is highly repeatable.

Baseline findings in the Collaborative Longitudinal Evaluation of Keratoconus (CLEK) Study.

PURPOSE: To describe the baseline findings in patients enrolled in the Collaborative Longitudinal Evaluation of Keratoconus (CLEK) Study. METHODS: This is a longitudinal observational study of 1209 patients with keratoconus enrolled at 16 clinical centers. Its main outcome measures are corneal scarring, visual acuity, keratometry, and quality of life. RESULTS: The CLEK Study patients had a mean age of 39.29+/-10.90 years with moderate to severe disease, assessed by a keratometric-based criterion (95.4% of patients had steep keratometric readings of at least 45 D) and relatively good visual acuity (77.9% had best corrected visual acuity of at least 20/40 in both eyes). Sixty-five percent of the patients wore rigid gas-permeable contact lens, and most of those (73%) reported that their lenses were comfortable. Only 13.5% of patients reported a family history of keratoconus. None reported serious systemic diseases that had been previously reported to be associated with keratoconus. Many (53%) reported a history of atopy. Fifty-three percent had corneal scarring in one or both eyes. CONCLUSIONS: Baseline findings suggest that keratoconus is not associated with increased risk of connective tissue disease and that most patients in the CLEK Study sample represent mild to moderate keratoconus. Additional follow-up of at least 3 years will provide new information about the progression of keratoconus, identify factors associated with progression, and assess its impact on quality of life.

Repeatability and agreement of two corneal-curvature assessments in keratoconus: keratometry and the first definite apical clearance lens (FDACL). CLEK Study Group. Collaborative Longitudinal Evaluation of Keratoconus.

PURPOSE: This study was conducted to determine the agreement and test-retest repeatability of two methods for measuring corneal curvature in keratoconus: keratometry and the First Definite Apical Clearance Lens (FDACL). Our interest in the FDACL procedure stems from the important contact lens-fitting information and documentation of disease progression provided by the FDACL trial lenses and observation of fluorescein patterns. METHODS: The Collaborative Longitudinal Evaluation of Keratoconus (CLEK) Study is an observational study that has enrolled 1,209 keratoconus patients to characterize the progression of keratoconus, to determine factors associated with its progression, and to assess its impact on quality of life. Ten percent of the patients were randomly selected at baseline for a retest examination. The baseline examination, which included keratometry and FDACL, was repeated in this sample. The FDACL is the flattest lens in the standardized CLEK trial lens set that vaults the apex of the cone. FDACL provides an estimate of the sagittal height of the cone. RESULTS: The correlation of FDACL with the steep keratometric reading (r = 0.89; p = 0.0001) and the flat keratometric reading (r = 0.83; p = 0.0001) were high. Test-retest repeatability as measured by the intraclass correlation coefficient (ICC) was high: FDACL ICC, 0.97; steep keratometric reading ICC, 0.96; and flat keratometric reading ICC, 0.95. Test-retest repeatability of FDACL remained high in advanced disease. CONCLUSION: FDACL provides a repeatable new procedure for determining disease severity in keratoconus.

Visual acuity repeatability in keratoconus: impact on sample size. Collaborative Longitudinal Evaluation of Keratoconus (CLEK) Study Group.

PURPOSE: The purpose of this paper is to determine the repeatability of visual acuity measurement in keratoconus and to describe the impact of measurement repeatability on sample size. METHODS: Approximately 10% of a 1209 patient sample in the Collaborative Longitudinal Evaluation of Keratoconus (CLEK) Study were selected randomly for a Repeat CLEK Study Visit. Patients were tested at the 15 CLEK Participating Clinics. The test-retest sample consisted of 1 34 keratoconus patients who met the entry criteria of the CLEK Study. High and low contrast Bailey-Lovie visual acuity was measured with the patient's habitual visual correction (entrance visual acuity monocularly and binocularly), and with the best correction monocularly (either the patient's rigid contact lens and over-refraction, or with a CLEK Study trial lens and appropriate over-refraction) at two visits separated by a median of 90 days (range 22 to 268 days). RESULTS: The mean absolute differences between the number of letters correct at the two visits ranged from a low of 3.24 +/- 3.1 for entrance high contrast binocular acuity to a high of 5.48 +/- 5.1 for best corrected low contrast monocular acuity. Intraclass correlation coefficients ranged from 0.757 to 0.853. The visual acuity score was somewhat higher at the Repeat Visit than at the Baseline Visit when the examiners were different between visits. CONCLUSIONS: Given the variable vision reported by keratoconus patients, visual acuity in this sample was very repeatable. Repeatability was slightly poorer when different examiners tested visual acuity at the Baseline and Repeat Visits.

Feasibility of fitting contact lenses with apical clearance in keratoconus.

Despite the wide variety of rigid contact lens fitting philosophies for the visual correction of keratoconus, questions remain, including which approach-flat, divided support, or steep-contributes the most toward the preservation of a clear cornea. One goal of the Collaborative Longitudinal Evaluation of Keratoconus (CLEK) Pilot Study was to determine the feasibility of managing early keratoconus patients with apical clearance rigid contact lenses. Of 30 keratoconus patients identified with at least 1 nonscarred cornea, 17 patients (30 eyes) were randomly assigned to a steep lens fitting protocol. After trial fitting with a standardized lens design demonstrating minimum apical clearance, lenses were dispensed whose base curve was 0.2 mm steeper than the minimum apical clearance lens. Patients were re-evaluated on a quarterly schedule concluding at 12 months. Changes in keratometry between baseline and 12 months identified unequal steepening of the flat and steep corneal curvatures, suggestive of corneal molding. Best corrected rigid lens visual acuity measures illustrated no significant changes over the course of the study. Clinically significant corneal compromise was transiently observed in some patients. Only 1 of 22 eyes completing the pilot study and fitted with apical clearance developed mild corneal scarring.

Standardized rigid contact lens fitting protocol for keratoconus.

Keratoconus is typically managed by a variety of rigid contact lens fitting techniques and lens designs. The two most fundamental fitting techniques are apical corneal touch (including divided or three-point touch) and apical clearance. In the course of designing a multi-center study of keratoconus patients, a standardized keratoconus fitting protocol was developed. All contact lens parameter options are uniform except for base curve and secondary curve radii, which are determined by interpretation of fluorescein patterns using the CLEK Study trial lens set and protocol. The initial trial lens's base curve is the average keratometric reading; sequentially steeper lenses are applied until definite apical clearance is observed. We have evaluated the feasibility of this standardized fitting protocol on 30 keratoconus patients. Our results suggest that we have developed a standardized contact lens fitting set and fitting protocol to simplify contact lens management in patients with mild to moderate keratoconus.

Photodocumentation of corneal scarring. Collaborative Longitudinal Evaluation of Keratoconus Study Group.

PURPOSE: A standardized system for photodocumenting corneal scars and for evaluating these photographs does not exist and is essential for clinical research. To address this need, we developed a system for photographing and evaluating corneal scars. METHODS: In the "Development Phase," we tested several procedures in small samples totaling 40 eyes of 20 keratoconus patients. In the "Test Phase," we used an independent sample of 150 eyes of 82 keratoconus patients. Fifty-nine of these 150 eyes had corneal scars, and 91 of the eyes did not as determined by the clinician. RESULTS: The photography protocol requires four central parallelepiped and two whole cornea oblique photographs after pupil dilation. With the clinician as gold standard, this technique yielded sensitivity of 96% and specificity of 83%. Evaluation of the corneal photographs as to the presence or absence of corneal scarring was performed independently by two masked readers. Agreement between clinicians on the presence of corneal scarring was 0.99 (kappa); agreement between readers for the presence of scarring was 0.80 (kappa). CONCLUSIONS: The corneal photography protocol we describe is recommended for use in clinical investigations of cicatricizing corneal disease and appears robust enough to be used in multicenter studies.

Biomicroscopic signs and disease severity in keratoconus. Collaborative Longitudinal Evaluation of Keratoconus (CLEK) Study Group.

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 variable, 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 Vogt's striae, Fleischer's ring, and/or corneal scarring. Fifty-eight percent of the eyes in this group of patients had > or = 20/40 visual acuity with manifest refraction. Penetrating keratoplasty was reported in 12.3% of eyes. This prospective survey identifies the associates between the presence of Vogt's striae, Fleischer's ring, and/or corneal scarring and increasing steepness, as measured by keratometry.

The effect of poor compliance and treatment side effects on sample size requirements in randomized clinical trials.

Treatment side effects and associated noncompliance have methodological implications vital to the testing of new drugs. In this paper, we quantify the impact of these factors on sample size requirements in clinical trials. In the Lipid Research Clinics Trial, side effects caused treatment group compliance (50.8%) to be lower than placebo compliance (67.3%). Cholesterol reduction among treatment noncompliers was 35.2% of the reduction among compliers. Had treatment group compliance been as high as placebo compliance, 41% fewer patients would have been required to achieve the same statistical power and an expected 31% more coronary events would have been prevented. We conclude: Because they discourage patient compliance, treatment side effects can (1) cause large sample size increases, (2) lead to underestimates of true efficacy, and (3) contribute to potentially invalid negative conclusions in clinical trials. The impact of side effects goes well beyond the complications and patient discomforts with which they are associated.

Postcataract ptosis. A randomized, double-masked comparison of peribulbar and retrobulbar anesthesia.

PURPOSE: A randomized, double-masked study of 317 patients was conducted to determine if the incidence of postcataract ptosis is greater with retrobulbar or two-injection peribulbar injection anesthesia. METHODS: Surgery consisted of a planned extracapsular extraction with posterior chamber lens implantation, and no superior rectus bridle suture was used. Ptosis was quantitatively documented preoperatively and postoperatively at 1, 2, 5, and 90 days by the surgeon, photographically at 90 days by a masked observer, and subjectively by the patients. Postcataract ptosis was defined as a drop in the lid margin of 2 mm or greater after correcting for any change in the fellow eye. RESULTS: The incidence of ptosis at 90 days in patients given peribulbar anesthesia was 5.8% and in patients given retrobulbar anesthesia 5.5%, and this difference was not statistically significant (P = 0.90). Eighteen percent of patients in both groups reported a change in the appearance of their eyelids. There was a moderate, positive correlation among patients who reported a change in their lid position and objective measurements of ptosis. Preoperative clinical measurements of vertical lid fissure width and levator function, and the appearance of the lid crease or superior sulcus were not predictive for the development of postoperative ptosis at 90 days; the best predictor was the presence of ptosis in the immediate postoperative period. CONCLUSION: The incidence of postcataract ptosis is the same whether two injection peribulbar or retrobulbar anesthesia is used.

Topical timolol administration reduces the incidence of glaucomatous damage in ocular hypertensive individuals. A randomized, double-masked, long-term clinical trial (1).

OBJECTIVES: A randomized, double-masked, 5-year clinical trial was conducted to determine whether topical timolol therapy was more effective than placebo in delaying or preventing the onset of glaucomatous damage in moderate-risk ocular hypertensive subjects. METHODS: One eye was chosen randomly to receive timolol therapy twice daily; the fellow eye received placebo (timolol vehicle). The primary end point of the study was reproducible visual field loss detected on three consecutive tests. Automated static threshold visual fields were added to the protocol as the study proceeded, and criteria for reproducible defects for the automated fields were developed. The secondary end point was progressive optic disc cupping confirmed by examination of stereoscopic disc photographs. Intraocular pressure was not used as an end point (i.e., eyes were not withdrawn from the study because they reached a predetermined level of intraocular pressure).