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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 μm. Twenty-four percent of the OHTS subjects had central corneal thickness > 600 μm. Mean central corneal thickness for African American subjects (555.7 ± 40.0 μm; n = 318) was 23 μm thinner than for white subjects (579.0 ± 37.0 μm; 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., (Copyright © 2020. Published by Elsevier Inc.)

Background: Estimating correlation coefficients among outcomes is one of the most important analytical tasks in epidemiological and clinical research. Availability of multivariate longitudinal data presents a unique opportunity to assess joint evolution of outcomes over time. Bivariate linear mixed model (BLMM) provides a versatile tool with regard to assessing correlation. However, BLMMs often assume that all individuals are drawn from a single homogenous population where the individual trajectories are distributed smoothly around population average., Methods: Using longitudinal mean deviation (MD) and visual acuity (VA) from the Ocular Hypertension Treatment Study (OHTS), we demonstrated strategies to better understand the correlation between multivariate longitudinal data in the presence of potential heterogeneity. Conditional correlation (i.e., marginal correlation given random effects) was calculated to describe how the association between longitudinal outcomes evolved over time within specific subpopulation. The impact of heterogeneity on correlation was also assessed by simulated data., Results: There was a significant positive correlation in both random intercepts (ρ = 0.278, 95% CI: 0.121-0.420) and random slopes (ρ = 0.579, 95% CI: 0.349-0.810) between longitudinal MD and VA, and the strength of correlation constantly increased over time. However, conditional correlation and simulation studies revealed that the correlation was induced primarily by participants with rapid deteriorating MD who only accounted for a small fraction of total samples., Conclusion: Conditional correlation given random effects provides a robust estimate to describe the correlation between multivariate longitudinal data in the presence of unobserved heterogeneity (NCT00000125).

Primary open angle glaucoma (POAG) is a chronic, progressive, irreversible, and potentially blinding optic neuropathy. The risk of blindness due to progressive visual field (VF) loss varies substantially from patient to patient. Early identification of those patients destined to rapid progressive visual loss is crucial to prevent further damage. In this article, a latent class growth model (LCGM) was developed to predict the binary outcome of VF progression using longitudinal mean deviation (MD) and pattern standard deviation (PSD). Specifically, the trajectories of MD and PSD were summarized by a functional principal component (FPC) analysis, and the estimated FPC scores were used to identify subgroups (latent classes) of individuals with distinct patterns of MD and PSD trajectories. Probability of VF progression for an individual was then estimated as weighted average across latent classes, weighted by posterior probability of class membership given baseline covariates and longitudinal MD/PSD series. The model was applied to the participants with newly diagnosed POAG from the Ocular Hypertension Treatment Study (OHTS), and the OHTS data was best fit by a model with 4 latent classes. Using the resultant optimal LCGM, the OHTS participants with and without VF progression could be accurately differentiated by incorporating longitudinal MD and PSD.

Background: Primary open-angle glaucoma (POAG) is one of the leading causes of blindness in the United States and worldwide. While lowering intraocular pressure (IOP) has been proven to be effective in delaying or preventing the onset of POAG in many large-scale prospective studies, one of the recent hot topics in glaucoma research is the effect of IOP fluctuation (IOP lability) on the risk of developing POAG in treated and untreated subjects., Method: In this paper, we analyzed data from the Ocular Hypertension Treatment Study (OHTS) and the European Glaucoma Prevention Study (EGPS) for subjects who had at least 2 IOP measurements after randomization prior to POAG diagnosis. We assessed the interrelationships among the baseline covariates, the changes of post-randomization IOP over time, and the risk of developing POAG, using a latent class analysis (LCA) which allows us to identify distinct patterns (latent classes) of IOP trajectories., Result: The IOP change in OHTS was best described by 6 latent classes differentiated primarily by the mean IOP levels during follow-up. Subjects with high post-randomization mean IOP level and/or large variability were more likely to develop POAG. Five baseline factors were found to be significantly predictive of the IOP classification in OHTS: treatment assignment, baseline IOP, gender, race, and history of hypertension. In separate analyses of EGPS, LCA identified different patterns of IOP change from those in OHTS, but confirmed that subjects with high mean level and large variability were at high risk to develop POAG., Conclusion: LCA provides a useful tool to assess the impact of post-randomization IOP level and fluctuation on the risk of developing POAG in patients with ocular hypertension. The incorporation of post-randomization IOP can improve the overall predictive ability of the original model that included only baseline risk factors.

Purpose: To determine if the accuracy of the baseline prediction model for the development of primary open-angle glaucoma (POAG) in patients with ocular hypertension can be improved by correcting intraocular pressure (IOP) for central corneal thickness (CCT)., Design: Reanalysis of the baseline prediction model for the development of POAG from the Ocular Hypertension Treatment Study (OHTS) substituting IOP adjusted for CCT using 5 different correction formulae for unadjusted IOP., Participants: A total of 1433 of 1636 participants randomized to OHTS who had complete baseline data for factors in the prediction model: age, IOP, CCT, vertical cup-to-disc ratio (VCDR), and pattern standard deviation (PSD)., Methods: Reanalysis of the prediction model for the risk of developing POAG using the same baseline variables (age, IOP, CCT, VCDR, and PSD) except that IOP was adjusted for CCT using correction formulae. A separate Cox proportional hazards model was run using IOP adjusted for CCT by each of the 5 formulae published to date. Models were run including and excluding CCT., Main Outcome Measures: Predictive accuracy of each Cox proportional hazards model was assessed using the c-statistic and calibration chi-square., Results: C-statistics for prediction models that used IOP adjusted for CCT by various formulas ranged from 0.75 to 0.77, no better than the original prediction model (0.77) that did not adjust IOP for CCT. Calibration chi-square was acceptable for all models. Baseline IOP, whether adjusted for CCT or not, was statistically significant in all models including those with CCT in the same model. The CCT was statistically significant in all models including those with IOP adjusted for CCT in the same model., Conclusions: The calculation of individual risk for developing POAG in ocular hypertensive individuals is simpler and equally accurate using IOP and CCT as measured, rather than applying an adjustment formula to correct IOP for CCT., (Copyright © 2012 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Primary open-angle glaucoma (POAG) is among the leading causes of blindness in the United States and worldwide. While numerous prospective clinical trials have convincingly shown that elevated intraocular pressure (IOP) is a leading risk factor for the development of POAG, an increasingly debated issue in recent years is the effect of IOP fluctuation on the risk of developing POAG. In many applications, this question is addressed via a "naïve" two-step approach where some sample-based estimates (e.g., standard deviation) are first obtained as surrogates for the "true" within-subject variability and then included in Cox regression models as covariates. However, estimates from two-step approach are more likely to suffer from the measurement error inherent in sample-based summary statistics. In this paper we propose a joint model to assess the question whether individuals with different levels of IOP variability have different susceptibility to POAG. In our joint model, the trajectory of IOP is described by a linear mixed model that incorporates patient-specific variance, the time to POAG is fit using a semi-parametric or parametric distribution, and the two models are linked via patient-specific random effects. Parameters in the joint model are estimated under Bayesian framework using Markov chain Monte Carlo (MCMC) methods with Gibbs sampling. The method is applied to data from the Ocular Hypertension Treatment Study (OHTS) and the European Glaucoma Prevention Study (EGPS), two large-scale multi-center randomized trials on the prevention of POAG.

In some clinical trials and epidemiologic studies, investigators are interested in knowing whether the variability of a biomarker is independently predictive of clinical outcomes. This question is often addressed via a naïve approach where a sample-based estimate (e.g., standard deviation) is calculated as a surrogate for the "true" variability and then used in regression models as a covariate assumed to be free of measurement error. However, it is well known that the measurement error in covariates causes underestimation of the true association. The issue of underestimation can be substantial when the precision is low because of limited number of measures per subject. The joint analysis of survival data and longitudinal data enables one to account for the measurement error in longitudinal data and has received substantial attention in recent years. In this paper we propose a joint model to assess the predictive effect of biomarker variability. The joint model consists of two linked sub-models, a linear mixed model with patient-specific variance for longitudinal data and a full parametric Weibull distribution for survival data, and the association between two models is induced by a latent Gaussian process. Parameters in the joint model are estimated under Bayesian framework and implemented using Markov chain Monte Carlo (MCMC) methods with WinBUGS software. The method is illustrated in the Ocular Hypertension Treatment Study to assess whether the variability of intraocular pressure is an independent risk of primary open-angle glaucoma. The performance of the method is also assessed by simulation studies.

Objective: To describe how much change, if any, occurs between central corneal thickness (CCT) measurements performed an average of 3.8 years apart in participants in the Ocular Hypertension Treatment Study (OHTS) and to identify clinical and demographic factors that are associated with changes in CCT, including baseline intraocular pressure, duration and class of ocular hypotensive medication, medical history, and systemic medication., Design: Secondary analysis of data from a randomized clinical trial., Participants: Ocular Hypertension Treatment Study participants. Participants who had undergone incisional intraocular or keratorefractive surgery between CCT measurements were excluded., Testing: The first CCT measurements were performed starting in 1999, and the second measurements were performed starting in 2002. Measurements were performed by OHTS certified technicians using an ultrasonic pachymeter under a standardized protocol., Main Outcome Measure: Central corneal thickness measurement (micrometers)., Results: First and second CCT measurements were available from 73% (1191) of the 1636 OHTS participants randomized. Central corneal thickness decreased a mean rate of -0.74+/-3.5 microm/year between the first and second CCT measurements. The mean medication exposure between first and second CCT measurements in participants originally randomized to observation (n = 595) was 1.1+/-1.6 years, versus 5.0+/-2.7 years in participants originally randomized to medication (n = 596). Central corneal thickness decreased by a mean of 1.0+/-3.4 microm/year among participants originally randomized to observation, compared with 0.5+/-3.5 microm/year among participants originally randomized to medication (P<0.0001). Subgroup analyses suggest that participants treated only with topical prostaglandin analogues (PGAs) between the two CCT measurements had a greater rate of decrease per year than participants treated only with topical beta-blockers., Conclusions: The rate of CCT decrease over 3.8 years is comparable to the cross-sectional age differences reported in the OHTS at the first measurement (0.6 microm/year) and comparable to other cross-sectional studies. Use of topical PGAs may be associated with a slightly higher rate of thinning. The modest age- and drug-related rates of thinning observed are unlikely to influence tonometry or clinical decision-making substantially in most clinical situations.

Objective: To compare the intraocular pressure (IOP) responses of self-identified African American and white participants in the Ocular Hypertension Treatment Study to therapeutic trials of topical, nonselective beta-adrenergic antagonists or prostaglandin analogues., Methods: Multivariate models that adjusted for baseline IOP and corneal thickness were used to estimate IOP response by race. Participants included 536 who were prescribed topical beta-adrenergic antagonists and 191 who were prescribed prostaglandin analogues, 25% of whom were African American., Main Outcome Measure: Intraocular pressure response in the ipsilateral eye after 4 to 6 weeks of a therapeutic trial., Results: Intraocular pressure response to nonselective beta-adrenergic antagonists did not differ between African American and white participants. Intraocular pressure response to prostaglandin analogues was slightly greater in African American participants, but this difference was not statistically significant. With both classes of medication, greater IOP reduction was associated with higher baseline IOP and thinner central corneal measurement., Conclusions: We found no statistically significant differences in IOP response to topical, nonselective beta-adrenergic antagonists or prostaglandin analogues between self-identified African American and white individuals. Application to Clinical Practice Studies of IOP response to medication should statistically adjust for baseline IOP and central corneal thickness. Clinicians should consider factors other than ethnicity when choosing an ocular hypotensive medication for a patient., Trial Registration: clinicaltrials.gov Identifier: NCT00000125.

Objective: To test the validity and generalizability of the Ocular Hypertension Treatment Study (OHTS) prediction model for the development of primary open-angle glaucoma (POAG) in a large independent sample of untreated ocular hypertensive individuals and to develop a quantitative calculator to estimate the 5-year risk that an individual with ocular hypertension will develop POAG., Design: A prediction model was developed from the observation group of the OHTS and then tested on the placebo group of the European Glaucoma Prevention Study (EGPS) using a z statistic to compare hazard ratios, a c statistic for discrimination, and a calibration chi2 for systematic overestimation/underestimation of predicted risk. The 2 study samples were pooled to increase precision and generalizability of a 5-year predictive model for developing POAG., Participants: The OHTS observation group (n = 819; 6.6 years' median follow-up) and EGPS placebo group (n = 500; 4.8 years' median follow-up)., Testing: Data were collected on demographic characteristics, medical history, ocular examination visual fields (VFs), and optic disc photographs., Main Outcome Measure: Development of reproducible VF abnormality or optic disc progression as determined by masked readers and attributed to POAG by a masked end point committee., Results: The same predictors for the development of POAG were identified independently in both the OHTS observation group and the EGPS placebo group-baseline age, intraocular pressure, central corneal thickness, vertical cup-to-disc ratio, and Humphrey VF pattern standard deviation. The pooled multivariate model for the development of POAG had good discrimination (c statistic, 0.74) and accurate estimation of POAG risk (calibration chi2, 7.05)., Conclusions: The OHTS prediction model was validated in the EGPS placebo group. A calculator to estimate the 5-year risk of developing POAG, based on the pooled OHTS-EGPS predictive model, has high precision and will be useful for clinicians and patients in deciding the frequency of tests and examinations during follow-up and advisability of initiating preventive treatment.

Purpose: To compare the rates of detection of optic disc hemorrhages by clinical examination and by review of optic disc photographs at the Optic Disc Reading Center (ODRC), to assess the incidence of and the predictive factors for disc hemorrhages in the annual disc photographs of the Ocular Hypertension Treatment Study (OHTS), and to determine whether optic disc hemorrhages predict the development of primary open-angle glaucoma (POAG) in the OHTS., Design: Cohort study., Participants: Three thousand two hundred thirty-six eyes of 1618 participants., Methods: Both eyes of participants were examined for optic disc hemorrhages every 6 months by clinical examination, with dilated fundus examinations every 12 months, and by annual review of stereoscopic disc photographs at the ODRC., Main Outcome Measures: Incidence of optic disc hemorrhages and POAG end points., Results: Median follow-up was 96.3 months. Stereophotography-confirmed glaucomatous optic disc hemorrhages were detected in 128 eyes of 123 participants before the POAG end point. Twenty-one cases (16%) were detected by both clinical examination and review of photographs, and 107 cases (84%) were detected only by review of photographs (P<0.0001). Baseline factors associated with disc hemorrhages were older age, thinner corneas, larger vertical cup-to-disc ratio, larger pattern standard deviation index on perimetry, family history of glaucoma, and smoking status. The occurrence of a disc hemorrhage increased the risk of developing POAG 6-fold in a univariate analysis (P<0.001; 95% confidence interval, 3.6-10.1) and 3.7-fold in a multivariate analysis that included baseline factors predictive of POAG (P<0.001; 95% confidence interval, 2.1-6.6). The 96-month cumulative incidence of POAG in the eyes without optic disc hemorrhage was 5.2%, compared with 13.6% in the eyes with optic disc hemorrhage. In eyes with a disc hemorrhage in which a POAG end point developed, the median time between the 2 events was 13 months., Conclusions: Review of stereophotographs was more sensitive at detecting optic disc hemorrhage than clinical examination. The occurrence of an optic disc hemorrhage was associated with an increased risk of developing a POAG end point in participants in the OHTS. However, most eyes (86.7%) in which a disc hemorrhage developed have not experienced a POAG end point to date.

Purpose: To determine whether topical ocular hypotensive medication is associated with refractive changes, visual symptoms, decreased visual function, or increased lens opacification., Design: Multi-center clinical trial., Methods: We compared the medication and observation groups of the Ocular Hypertension Treatment Study (OHTS) during 6.3 years of follow-up with regard to the rate of cataract and combined cataract/filtering surgery, and change from baseline in visual function, refraction, and visual symptoms. A one-time assessment of lens opacification was done using the Lens Opacities Classification System III (LOCS III) grading system., Results: An increased rate of cataract extraction and cataract/filtering surgery was found in the medication group (7.6%) compared with the observation group (5.6%) (hazard ratio [HR] 1.56; 95% confidence interval [CI] 1.05 to 2.29). The medication and observation groups did not differ with regard to changes from baseline to June 2002 in Humphrey visual field mean deviation, Humphrey visual field foveal sensitivity, Early Treatment of Diabetic Retinopathy Study (ETDRS) visual acuity, refraction, and visual symptoms. For the medication and observation groups, LOCS III readings were similar for nuclear color, nuclear opalescence, and cortical opacification. There was a borderline higher mean grade for posterior subcapsular opacity in the medication group (0.43 +/- 0.6 SD) compared with the observation group (0.36 +/- 0.6 SD) (P = .07)., Conclusions: We noted an increased rate of cataract extraction and cataract/filtering surgery in the medication group as well as a borderline higher grade of posterior subcapsular opacification in the medication group on LOCS III readings. We found no evidence for a general effect of topical ocular hypotensive medication on lens opacification or visual function.

Objective: To determine whether baseline confocal scanning laser ophthalmoscopy (CSLO) optic disc topographic measurements are associated with the development of primary open-angle glaucoma (POAG) in individuals with ocular hypertension., Methods: Eight hundred sixty-five eyes from 438 participants in the CSLO Ancillary Study to the Ocular Hypertension Treatment Study with good-quality baseline CSLO images were included in this study. Each baseline CSLO parameter was assessed in univariate and multivariate proportional hazards models to determine its association with the development of POAG., Results: Forty-one eyes from 36 CSLO Ancillary Study participants developed POAG. Several baseline topographic optic disc measurements were significantly associated with the development of POAG in both univariate and multivariate analyses, including larger cup-disc area ratio, mean cup depth, mean height contour, cup volume, reference plane height, and smaller rim area, rim area to disc area, and rim volume. In addition, classification as "outside normal limits" by the Heidelberg Retina Tomograph classification and the Moorfields Regression Analysis classifications (overall, global, temporal inferior, nasal inferior, and superior temporal regions) was significantly associated with the development of POAG. Within the follow-up period of this analysis, the positive predictive value of CSLO indexes ranged from 14% (Heidelberg Retina Tomograph classification and Moorfields Regression Analysis overall classification) to 40% for Moorfields Regression Analysis temporal superior classification., Conclusions: Several baseline topographic optic disc measurements alone or when combined with baseline clinical and demographic factors were significantly associated with the development of POAG among Ocular Hypertension Treatment Study participants. Longer follow-up is required to evaluate the true predictive accuracy of CSLO measures.

Purpose: To determine whether central corneal thickness (CCT) correlates with measured intraocular pressure (IOP) response to topical ocular hypotensive medication in the Ocular Hypertension Treatment Study (OHTS)., Design: Prospective randomized clinical trial., Methods: Intraocular pressure measurements were performed by Goldmann applanation tonometry. Central corneal thickness was measured by ultrasonic pachymetry. The following indicators of IOP response to topical ocular hypotensive medication were examined: (1) IOP after an initial four- to six-week one-eyed therapeutic trial of a nonselective beta-blocker (N = 549) or a prostaglandin analog (N = 201); (2) the mean IOP response during 12 to 60 months of follow-up among medication participants (N = 689); (3) the percentage of follow-up visits at which both eyes met the treatment goal; (4). the total number of different medications prescribed to reach treatment goal; and (5) the total number of different medications prescribed multiplied by the number of months each medication was prescribed., Results: Central corneal thickness was inversely related to the IOP response after the initial one-eyed therapeutic trial and during 12 to 60 months of follow-up (P < .05). Mean CCT was not correlated with the number of different medications prescribed during follow-up, the total medication-months, or the percentage of visits at which IOP target was met., Conclusions: Individuals with thicker corneas had smaller measured IOP responses to ocular hypotensive medication than those with normal or thin corneas. We believe that CCT measurements may be useful in patient management and in interpreting clinical trials of ocular hypotensive medication.

Purpose: Higher baseline pattern standard deviation (PSD) and larger vertical cup-to-disk ratio (VC/D) were factors in the predictive model for the development of primary open-angle glaucoma (POAG) in the Ocular Hypertension Treatment Study. Because early changes in PSD and VC/D may be indicative of early POAG damage, we repeated the prediction model excluding PSD and VC/D., Design: Reanalysis of baseline factors for the development of POAG., Methods: We compared the hazard ratios for baseline factors predictive of POAG in the multivariate Cox proportional hazards model that included PSD and VC/D and in the model that excluded them., Results: Hazard ratios for baseline factors predictive of POAG in Ocular Hypertension Treatment Study were not substantially affected by the inclusion or exclusion of PSD and VC/D in the proportional hazards model., Conclusion: Whether PSD or VC/D was included in the Cox proportional hazards model, the same baseline factors were statistically significant and their hazard ratios were essentially similar.

Background: The prevalence of glaucoma is higher in African American individuals than in white individuals., Objective: To report the safety and efficacy of topical ocular hypotensive medication in delaying or preventing the onset of primary open-angle glaucoma (POAG) among African American participants in the Ocular Hypertension Treatment Study., Methods: Eligibility criteria included age between 40 and 80 years, intraocular pressure between 24 and 32 mm Hg in one eye and between 21 and 32 mm Hg in the other eye, and no evidence of glaucomatous structural or functional damage by standard clinical measures. Participants were randomized to either the observation group or medication group. Of the 1636 participants randomized, 408 were self-identified as African American., Main Outcome Measure: The primary outcome was the development of reproducible visual field abnormality and/or reproducible optic disc deterioration attributed to POAG., Results: Among African American participants, 17 (8.4%) of 203 in the medication group developed POAG during the study (median follow-up, 78 months) compared with 33 (16.1%) of 205 participants in the observation group (hazard ratio, 0.50; 95% confidence interval, 0.28-0.90; P =.02)., Conclusion: Topical ocular hypotensive therapy is effective in delaying or preventing the onset of POAG in African American individuals who have ocular hypertension.

Background: The Ocular Hypertension Treatment Study (OHTS) has shown that topical ocular hypotensive medication is effective in delaying or preventing the onset of primary open-angle glaucoma (POAG) in individuals with elevated intraocular pressure (ocular hypertension) and no evidence of glaucomatous damage., Objective: To describe baseline demographic and clinical factors that predict which participants in the OHTS developed POAG., Methods: Baseline demographic and clinical data were collected prior to randomization except for corneal thickness measurements, which were performed during follow-up. Proportional hazards models were used to identify factors that predicted which participants in the OHTS developed POAG., Results: In univariate analyses, baseline factors that predicted the development of POAG included older age, race (African American), sex (male), larger vertical cup-disc ratio, larger horizontal cup-disc ratio, higher intraocular pressure, greater Humphrey visual field pattern standard deviation, heart disease, and thinner central corneal measurement. In multivariate analyses, baseline factors that predicted the development of POAG included older age, larger vertical or horizontal cup-disc ratio, higher intraocular pressure, greater pattern standard deviation, and thinner central corneal measurement., Conclusions: Baseline age, vertical and horizontal cup-disc ratio, pattern standard deviation, and intraocular pressure were good predictors for the onset of POAG in the OHTS. Central corneal thickness was found to be a powerful predictor for the development of POAG.

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.

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.

Objective: To determine the effect of combined finasteride and flutamide therapy on haemoglobin and haematocrit values in men with advanced prostate cancer., Patients and Methods: Nineteen men, previously untreated by hormone therapy, with histologically confirmed adenocarcinoma of the prostate and clinical evidence of advanced disease, were treated with combined finasteride (5 mg/day) and flutamide (750 mg/day) for at least 6 months. Complete blood counts were performed before initiation and after 6 months of therapy., Results: After 6 months of finasteride and flutamide therapy both haemoglobin levels and haematocrit decreased in all men, with a mean (sd, range) decrease of 16 (10, 3-42) g/L and 4.6 (2.7, 0.8-9.9)%, respectively., Conclusion: Combined finasteride and flutamide therapy significantly lowers haemoglobin and haematocrit levels in men with advanced prostate cancer, and further study of this effect is warranted.

Purpose: We examined the usefulness of measurements of free prostate specific antigen (PSA) and PSA density for predicting prostate cancer in men who had had a prior negative biopsy, a serum PSA level of 4.1 to 10.0 ng./ml. and benign findings on prostate examination., Materials and Methods: We measured percent free serum PSA and PSA density in 163 male volunteers age 50 years or older who were advised to have repeat prostatic biopsies for a serum PSA level of 4.1 to 10.0 ng./ml., Results: Of 99 men who had repeat biopsies 20 (20%) had prostate cancer detected. Prostate cancer was significantly associated with lower free PSA level and higher PSA density, with overlap in 83% of the cases. The use of percent free PSA cutoffs of 28 and 30% would have detected 90 and 95% of cancers, respectively, and avoided 13 and 12% of the biopsies, respectively. PSA density cutoffs of 0.10 and 0.08 would have detected 90 and 95% of cancers, respectively, and avoided 31 and 12% of biopsies, respectively., Conclusions: Free PSA and PSA density predict prostate cancer in men who have had prior negative prostatic biopsies, serum PSA levels of 4.1 to 10.0 ng./ml. and a benign prostate examination. Both parameters may be used to avoid unnecessary biopsies with an acceptable decrease in sensitivity. Further studies are needed to determine cutoffs to be used in clinical practice.