Laurie LaBree

The Role of Carotid Arterial Intima-Media Thickness in Predicting Clinical Coronary Events

Carotid arterial intima-media thickness measured with B-mode ultrasonography is used as a noninvasive end point (that is, an outcome) in epidemiologic studies and clinical trials to gauge progression and regression of atherosclerosis [1-3]. As such, carotid arterial intima-media thickness, expressed as a single measurement (in millimeters) or a rate of change (in millimeters per year), is used as a surrogate end point for atherosclerosis of the coronary artery. However, its relation to coronary events has not been fully explored. It is well established that progression of atherosclerosis of the coronary artery determined by sequential coronary angiography is predictive of coronary events [4-6]. A close histologic relation between carotid and coronary atherosclerosis has been seen in autopsy studies [7], and the two arterial beds share many risk factors that contribute to the progression of atherosclerosis [8, 9]. Furthermore, carotid arterial intima-media thickness has been a good indicator of the presence and extent of coronary artery disease in observational studies [10, 11]. The Cholesterol Lowering Atherosclerosis Study [12] was a clinical arterial imaging trial designed to study the effects of colestipol-niacin therapy on progression of atherosclerosis in the coronary, femoral, and carotid arteries. We have reported that treatment is beneficial for all three arterial beds [3, 13-16]. In addition, long-term follow-up of the study cohort indicated that progression of coronary artery disease was predictive of coronary events [4]. The objectives of this long-term follow-up of the Cholesterol Lowering Atherosclerosis Study cohort are 1) to determine whether carotid arterial intima-media thickness [expressed as a single measurement or as a rate of change] predicts coronary events, 2) to compare the relative prognostic utility of the two carotid arterial intima-media thickness measures; and 3) to compare the relative prognostic contribution of the two carotid arterial intima-media thickness measures with an angiographic measure of coronary artery disease progression and lipid levels. Methods Study Design In the Cholesterol Lowering Atherosclerosis Study, 188 nonsmoking men 40 to 59 years of age who had previously had coronary artery bypass graft surgery were randomly assigned to receive colestipol-niacin therapy plus dietary therapy (target diet, <125 mg of cholesterol per day and 22% of energy as fat, 10% as polyunsaturated fat, and 4% as saturated fat) or placebo plus dietary therapy (target diet, <250 mg of cholesterol per day and 26% of energy as fat, 10% as polyunsaturated fat, and 5% as saturated fat) [12]. In addition to the primary end point provided by coronary angiograms at baseline and after 2 years of treatment, B-mode ultrasonography of the carotid artery was done at baseline and every 6 months during the 2-year treatment period. The cohort for this study consisted of patients who had completed the 2-year treatment period and had evaluable coronary and carotid arterial end points. Baseline and 2-year coronary artery films were processed by quantitative coronary angiography in tandem; frames were matched for orientation and degree of contrast filling [17]. For each evaluable arterial segment, three sequential frames were processed in end diastole. For each coronary lesion, percent diameter stenosis was obtained as the average over the three sequential frames. For each patient, the change in percent diameter stenosis over 2 years was averaged for all evaluable coronary artery lesions. B-mode ultrasonographic images of the carotid artery were obtained with a Diasonics CV400 system with a 7.5-MHz probe (Diasonics, Milpetas, California). Longitudinal views of the far wall of the right distal common carotid artery were recorded with the minimum gain necessary for clear visualization of structures. Common carotid arterial intima-media thickness was measured with an automated computerized edge-detection algorithm [18]. The distance between the echoes arising from the blood-intima interface and the media-adventitia interface was taken as the measure of intima-media thickness. Distal common carotid arterial intima-media thickness was the average of approximately 80 intima-media thickness measurements made over 1 cm. Measurements were made by persons blinded to treatment assignment and the occurrence of clinical coronary events. Follow-up for Coronary Events After completion of the 2-year treatment period, the occurrence of major medical events and information on all medications (including lipid-lowering agents) was determined for all patients by a clinic visit (59% of all follow-ups) or a mailed questionnaire (41%) at annual follow-up points through 30 June 1994. No ascertainment bias was associated with method of follow-up. Coronary events were nonfatal acute myocardial infarction, coronary death, and need for coronary artery revascularization [percutaneous transluminal coronary angioplasty or coronary artery bypass graft surgery] because of recurrence or worsening of angina pectoris. For all patient-reported events, hospital records were obtained for confirmation, and all causes of death were confirmed by hospital records and death certificates. Myocardial infarction was diagnosed by a cardiologist who was blinded to treatment assignment and ultrasonographic and angiographic end point measures. Myocardial infarction was confirmed if two of the following three criteria were substantiated: typical chest pain, positive creatine phosphokinase-MB, and a new Q wave on electrocardiogram. In order to include only events that were clearly related to clinical symptoms, we did not count 1) coronary artery revascularizations that were related to the reading of the 2-year coronary angiogram or 2) silent myocardial infarctions noted on electrocardiograms at annual follow-up examinations as clinical coronary events. Statistical Analysis The two dependent variables were time from completion of the trial to nonfatal myocardial infarction or coronary death and time from completion of the trial to the first coronary event (nonfatal myocardial infarction, coronary death, or coronary artery revascularization). The two independent variables were the absolute carotid arterial intima-media thickness (in millimeters), measured at the end of the 2-year trial, and the annual rate of change in carotid arterial intima-media thickness (in millimeters per year), evaluated over the 2-year trial. The intima-media thickness change rate was computed for each patient by fitting a least-squares regression line relating intima-media thickness measurements to time in the study. The average number of ultrasonographic examinations per patient was 2.8 0.4. The absolute carotid arterial intima-media thickness is a cumulative measure of carotid atherosclerosis, whereas the intima-media thickness change rate represents the speed with which atherosclerosis of the carotid artery is changing. Univariate and multivariate proportional hazards models were used to test for relations (overall and within each treatment group) between the intima-media thickness variables and coronary event rates. Covariates included the baseline value for intima-media thickness (for analyses of intima-media thickness change rates) and treatment group (for analyses of the total sample). Because patients had the option to continue their randomized, blinded treatment in a 2-year extension of the Cholesterol Lowering Atherosclerosis Study, an additional covariate indexed whether a given patient was treated in the 2-year extension period. Likelihood ratio tests for trend in coronary event rates used each intima-media thickness variable as continuous data. Hazard ratios (as estimators of relative risks) and 95% CIs were expressed per SD (0.03 mm/year for the carotid arterial intima-media thickness change rate and 0.13 mm for the absolute carotid arterial intima-media thickness). Absolute carotid arterial intima-media thickness values were categorized by quartiles based on the distribution of the baseline intima-media thickness for all patients; carotid arterial intima-media thickness change rates were categorized by quartiles based on the distribution of changes in the placebo group. Hazard ratios were then computed for each of the upper quartiles relative to the first. Because earlier analyses of the study cohort showed a significant relation between progression of coronary artery disease (assessed by the change in percent diameter stenosis using quantitative coronary angiography) and coronary events [4], we also evaluated the relative prognostic contributions of this angiographic measure of coronary artery disease progression and the ultrasonographic measure of carotid arterial intima-media thickness progression. For the change in percent diameter stenosis, hazard ratios and 95% CIs were expressed per 10% change in percent diameter stenosis. The cutoff of 10% change is double the measurement error for percent diameter stenosis on short-term repeated angiography. The joint prognostic contribution of the carotid artery and coronary artery measures of atherosclerosis with lipid levels that were found to be significantly different between patients with and without coronary events was also evaluated. Values given are the mean SD unless otherwise indicated. Role of the Funding Source The authors were responsible for data collection, data management, statistical analyses, and data interpretation. Research was supported by the National Heart, Lung, and Blood Institute through investigator-initiated grants to Dr. Hodis (RO1-HL-49885) and Dr. Mack (RO3-HL-54532). The funding source had no role in deciding whether the study would be submitted for publication. Results Characteristics of the Cohort at Baseline and after Treatment Of the 188 patients randomly assigned to treatment, 42 (22%) were excluded from the study: Eleven did not have a baseline ultrasonogram, 13 had no ultrasonographic fo

Ambient air pollution and atherosclerosis in Los Angeles.

Associations have been found between long-term exposure to ambient air pollution and cardiovascular morbidity and mortality. The contribution of air pollution to atherosclerosis that underlies many cardiovascular diseases has not been investigated. Animal data suggest that ambient particulate matter (PM) may contribute to atherogenesis. We used data on 798 participants from two clinical trials to investigate the association between atherosclerosis and long-term exposure to ambient PM up to 2.5 μm in aerodynamic diameter (PM2.5). Baseline data included assessment of the carotid intima-media thickness (CIMT), a measure of subclinical atherosclerosis. We geocoded subjects’ residential areas to assign annual mean concentrations of ambient PM2.5. Exposure values were assigned from a PM2.5 surface derived from a geostatistical model. Individually assigned annual mean PM2.5 concentrations ranged from 5.2 to 26.9 μg/m3 (mean, 20.3). For a cross-sectional exposure contrast of 10 μg/m3 PM2.5, CIMT increased by 5.9% (95% confidence interval, 1–11%). Adjustment for age reduced the coefficients, but further adjustment for covariates indicated robust estimates in the range of 3.9–4.3% (p-values, 0.05–0.1). Among older subjects (≥60 years of age), women, never smokers, and those reporting lipid-lowering treatment at baseline, the associations of PM2.5 and CIMT were larger with the strongest associations in women ≥60 years of age (15.7%, 5.7–26.6%). These results represent the first epidemiologic evidence of an association between atherosclerosis and ambient air pollution. Given the leading role of cardiovascular disease as a cause of death and the large populations exposed to ambient PM2.5, these findings may be important and need further confirmation.

Triglyceride- and cholesterol-rich lipoproteins have a differential effect on mild/moderate and severe lesion progression as assessed by quantitative coronary angiography in a controlled trial of lovastatin.

BACKGROUNDThe Monitored Atherosclerosis Regression Study, a randomized, double-blind, placebo-controlled, 2-year trial of lovastatin monotherapy, found that coronary lesions or = 50% S at baseline had different responses to therapy. We now report on clinical, lipid, and nonlipid risk factors of treatment response in these lesion subsets.METHODS AND RESULTSTwo hundred seventy subjects, 37 to 67 years old, with plasma total cholesterol (TC) 190 to 295 mg/dL (4.91 to 7.63 mmol/L) and total triglyceride or = 50% S) lesions in 220 angiogram pairs analyzed by computer quantitative coronary angiography. In the placebo group, risk factors (P < .05) for the progression of mild/moderate lesions were trig...

Reduction in Carotid Arterial Wall Thickness Using Lovastatin and Dietary Therapy: A Randomized, Controlled Clinical Trial

Controlled clinical trials to assess the effects of therapy for atherosclerosis have generally used either clinical cardiovascular events or serial arterial imaging as end points. Serial coronary angiographic assessment of lesion change has been the most commonly used end point in arterial imaging trials [1]. Evidence now indicates that high-resolution B-mode ultrasonographic measurement of the combined thickness of the carotid arterial intima-media complex is a reliable end point for lipid-lowering interventional trials [1]. Unlike angiographic imaging procedures that focus on changes in the lumen, noninvasive imaging of the arterial wall 1) directly quantifies the response of early atherosclerotic changes to risk-factor modification, 2) can be done as often as necessary in symptomatic or asymptomatic patients of any age, and 3) carries negligible risk [2]. In addition, the measurement of distal common carotid arterial far wall intima-media thickness (carotid arterial intima-media thickness) by automated computerized edge detection varies less than angiographic measurement of the coronary arteries; therefore, a much smaller sample size is needed to show a therapeutic effect [1, 3-5]. The Cholesterol Lowering Atherosclerosis Study (CLAS), a randomized, placebo-controlled, serial arterial imaging clinical trial [6], was designed to comprehensively survey the effects of colestipol-niacin plus dietary therapy on the progression of atherosclerosis in the coronary [7-9], femoral [10], and carotid arterial beds [3, 4]. That study was the first randomized, controlled clinical trial to provide evidence for a drug-induced reduction in carotid arterial intima-media thickness using B-mode ultrasonographic imaging as an outcome measurement of change in early, preintrusive atherosclerosis (the stage at which atherosclerosis is limited to the arterial wall and does not intrude into the arterial lumen) [3, 4]. The serial ultrasonographic results showed the powerful advantage of modeling sequential change over time [4]. The Monitored Atherosclerosis Regression Study (MARS) was a randomized, double-blind, placebocontrolled, serial arterial imaging clinical trial in which carotid arterial intima-media thickness was measured every 6 months with B-mode ultrasonography. Similar in design to CLAS, MARS was an independent clinical trial that showed that lovastatin plus dietary therapy reduced the progression of lesions of the coronary arteries as determined by both visual assessment of coronary artery change and quantitative coronary angiography [11, 12]. The ultrasonographic methods and findings from CLAS were replicated in a subgroup of 30 patients from MARS who, like the CLAS participants, were nonsmoking men who had had coronary arterial bypass grafts [1]. In this paper, we extend the findings of these studies to the complete cohort of patients from MARS with serial carotid arterial ultrasonographic measurements. We report evidence of benefit from lovastatin plus dietary therapy on early, preintrusive atherosclerosis through the measurement of change in the carotid arterial intima-media thickness in 188 patients evaluated every 6 months for as long as 4 years. We also relate these changes in early atherosclerosis to clinical, lipid, lipoprotein, and apolipoprotein risk factors for atherosclerosis. Methods Design of the Monitored Atherosclerosis Regression Study This study was a randomized, double-blind, placebo-controlled serial coronary angiographic and carotid arterial ultrasonographic imaging clinical trial that has been described previously [12]. Two hundred seventy patients (91% male, smokers and nonsmokers, 37 to 67 years of age) with total serum cholesterol levels between 4.92 and 7.64 mmol/L (190 mg/dL to 295 mg/dL) were randomly assigned to receive either lovastatin, 80 mg/d, or placebo. Two hundred fifteen patients were at the University of Southern California, and 55 were at the University of Wisconsin. The lovastatin group and the placebo group had identical dietary goals: no more than 250 mg of cholesterol per day, 27% of energy as total fat calories, 7% of energy as saturated fat calories, 10% of energy as monounsaturated fat calories, and 10% of energy as polyunsaturated fat calories. All patients had angiographically confirmed coronary artery disease in at least two segments with at least a 50% stenosis. Coronary angiography was done under standardized conditions at baseline and at 2 and 4 years after randomization; the 2-year results have been reported previously [11]. The 215 patients at the University of Southern California also had B-mode carotid ultrasonography, the results of which were used to measure carotid arterial intima-media thickness at baseline and every 6 months throughout the trial. Of these 215 patients, 196 (91%) had angiography at 2 years; 58% of the patients (77 receiving lovastatin and 48 receiving placebo) agreed to participate in an optional, double-blind, 2-year extension of the original randomized trial. An independent External Data and Safety Monitoring Committee recommended discontinuing the 2-year extension because of the observed treatment benefit in the per-patient reduction in stenosis for high-grade lesions as determined by quantitative coronary angiography, and in a panel assessment of overall change in coronary artery lesions [11]. Sixty-nine (32%) of the 215 patients at the University of Southern California had angiography at 4 years. Patients in the lovastatin group who participated in the 2-year extension had on-trial lipid levels, coronary artery end points, and rates of change in carotid arterial intima-media thickness similar to those of the treated patients who chose not to participate in the extension. Patients in the placebo group who chose not to participate in the extension had poorer coronary outcome at 2 years than did the patients who participated (P = 0.02), but both participants and nonparticipants had similar on-trial lipid levels and equivalent rates of change in carotid arterial intima-media thickness (0.02 0.04 mm/y). Lipid, Lipoprotein, and Apolipoprotein Levels Total serum cholesterol and total serum triglyceride levels were measured using an enzymatic method under the Standardization Program of the National Centers for Disease Control and Prevention; patients fasted 8 hours before samples for analysis were collected. High-density lipoprotein (HDL) cholesterol levels were measured after apolipoprotein B-containing lipoproteins were precipitated in whole plasma with heparin manganese chloride. Low-density lipoprotein (LDL) cholesterol levels were estimated using the Friedewald equation [12, 13]. Plasma apolipoprotein A-I, B, C-III, and E levels [14-17] were measured using electroimmunoassay at the Oklahoma Medical Research Foundation. Apolipoprotein C-III levels were measured in whole plasma as well as in heparin manganese supernatants (apolipoprotein C-III-HS) and heparin manganese precipitates (apolipoprotein C-III-HP) as previously described [18]. Apolipoprotein C-III-HS approximates apolipoprotein C-III in HDL, and apolipoprotein C-III-HP approximates apolipoprotein C-III contained in very-low-density lipoprotein (VLDL) plus LDL. Lipid, lipoprotein, and apolipoprotein levels were measured at baseline, and then lipid levels were measured every 2 months and lipoprotein and apolipoprotein levels were measured every 4 months throughout the study. Ultrasonography and Image Analysis The methods for ultrasonography and image analysis for carotid arterial intima-media thickness and their reproducibility have been previously described [3, 5]. B-mode scanning was done with a Diasonics CV400 ultrasound system with a 7.5-MHz probe (Diasonics, Milpitas, California). Longitudinal views of the near wall and the far wall of the right distal common carotid artery were recorded with the minimum gain needed to clearly visualize structures. An image analyst, blinded to treatment assignment, measured the distal common carotid arterial far wall intima-media thickness by automated computerized edge detection using a 386/33 PC computer equipped with a Data Translation DT 2862 image-processing board (Data Translation, Marboro, Massachusetts). The automated computerized edge-finding algorithm results in closely spaced measurements of intima-media thickness, approximately 100 to 120 points/cm, from which the average intima-media thickness is determined. The distance between the echoes arising from the blood-intima interface and from the media-adventitia interface was taken as the measure of the intima-media thickness complex [19]. The computerized edge-detection method has been described previously [5]. Statistical Analysis We compared the clinical measures and lipid, lipoprotein, and apolipoprotein levels at baseline for patients with and those without carotid arterial ultrasonographic end point data. For patients with carotid arterial ultrasonographic end point data, we compared carotid arterial intima-media thickness at baseline, and clinical measures and lipid, lipoprotein, and apolipoprotein levels at baseline and on-trial in the treatment group with those in the placebo group. On-trial levels of these variables were computed as averages of all measurements made during the trial, weighted by the time interval between measurements. Significance testing was done using the Student t-test for independent samples, with the two-sided significance level set at 0.05. For each patient, we fit a least-squares regression line relating carotid arterial intima-media thickness to the time since baseline ultrasonography to estimate the annual rate of progression of carotid arterial intima-media thickness. Thus, the unit of analysis was a patient-specific annualized progression rate of intima-media thickness; mean progression rates were then compared between treatment groups. Because carotid arterial intima-media thickness differed significantly at baseline between the treatment groups, we

Alpha-Tocopherol Supplementation in Healthy Individuals Reduces Low-Density Lipoprotein Oxidation but Not Atherosclerosis The Vitamin E Atherosclerosis Prevention Study (VEAPS)

Background—Epidemiological studies have demonstrated an inverse relationship between vitamin E intake and cardiovascular disease (CVD) risk. In contrast, randomized controlled trials have reported conflicting results as to whether vitamin E supplementation reduces atherosclerosis progression and CVD events. Methods and Results—The study population consisted of men and women ≥40 years old with an LDL cholesterol level ≥3.37 mmol/L (130 mg/dL) and no clinical signs or symptoms of CVD. Eligible participants were randomized to DL-&agr;-tocopherol 400 IU per day or placebo and followed every 3 months for an average of 3 years. The primary trial end point was the rate of change in the common carotid artery far-wall intima-media thickness (IMT) assessed by computer image-processed B-mode ultrasonograms. A mixed effects model using all determinations of IMT was used to test the hypothesis of treatment differences in IMT change rates. Compared with placebo, &agr;-tocopherol supplementation significantly raised plasma vitamin E levels (P <0.0001), reduced circulating oxidized LDL (P =0.03), and reduced LDL oxidative susceptibility (P <0.01). However, vitamin E supplementation did not reduce the progression of IMT over a 3-year period compared with subjects randomized to placebo. Conclusions—The results are consistent with previous randomized controlled trials and extend the null results of vitamin E supplementation to the progression of IMT in healthy men and women at low risk for CVD.

A Randomized Trial Comparing Mitomycin C and Conjunctival Autograft After Excision of Primary Pterygium

PURPOSE To determine the rate of recurrence and complications after bare sclera excision of primary pterygia followed by low-dose mitomycin C (0.2 mg/ml twice daily for five days), placebo (balanced saline solution), or conjunctival autograft. METHODS We performed a prospective, double-masked clinical trial of 64 patients (60 Hispanic) randomly assigned to a treatment group. Twenty-four patients received mitomycin C, 23 conjunctival autograft, and 17 placebo. Recurrence was defined as fibrovascular tissue over the corneoscleral limbus onto clear cornea in the area of previous pterygium excision. RESULTS The recurrence rate after mitomycin C and conjunctival autograft was 38% and 39% of eyes, respectively, after mean follow-up (in recurrence-free patients) of 12.3 and 13.5 months, respectively. The recurrence rate after placebo treatment was significantly higher (P = .002), 88%, after mean follow-up (in recurrence-free patients) of 9.3 months. Increasing age was associated with significantly fewer recurrences (P = .006) after controlling for pterygium type (atrophic, noninflamed, or inflamed) and treatment group. The mean time to recurrence varied from 3.7 to 4.8 months; only 6% of recurrences were noted after the sixth postoperative month. Major complications included symblepharon (two), loose autograft (one), and pyogenic granuloma (two). No group had significantly more complications. CONCLUSIONS Conjunctival autograft and low-dose topical mitomycin C are equally effective as adjunctive treatment after excision of primary pterygia in this young, southern California, predominantly Hispanic population. Both methods have significantly lower rates of recurrence than bare sclera excision alone, and neither is associated with severe complications after one year of follow-up. Increasing patient age is associated with significantly less risk of recurrence.

Progression of Coronary Artery Disease Predicts Clinical Coronary Events Long-term Follow-up From the Cholesterol Lowering Atherosclerosis Study

BACKGROUND Progression of coronary artery disease is assumed to be a surrogate end point for clinical coronary events. Because no single method or measure for a coronary angiographic end point is uniformly accepted as optimal, the utility and validity of surrogate end points for predicting clinical coronary events remain unsettled. METHODS AND RESULTS The Cholesterol Lowering Atherosclerosis Study randomized 162 nonsmoking, 40- to 59-year-old men with previous coronary artery bypass graft surgery to colestipol/niacin plus diet or placebo plus diet. Atherosclerosis change on 2-year coronary angiograms was evaluated by a consensus panel and by quantitative coronary angiography (average per-subject change in percent diameter stenosis [%S] and minimum lumen diameter [MLD). With all three end points, the benefit of colestipol/niacin treatment on coronary artery atherosclerosis has been reported. Annual follow-up for an average of 7 years (range, 6.3 months to 10 years) has been carried out on all subjects who completed the 2-year angiogram. Clinical coronary events (need for revascularization, nonfatal acute myocardial infarction, and coronary death) have been documented. Risk of clinical coronary events was positively related to coronary lesion progression for all three surrogate end points (P<.05). New lesion formation in bypass grafts (P=.02) and progression of mild/moderate lesions ( < 50%S) were predictive of clinical coronary events (P<.01). Change in MLD contributed significantly to the prediction of clinical coronary events beyond a model with %S alone (P<.05). CONCLUSIONS In this population of nonsmoking men with previous bypass surgery, both the consensus panel- and quantitative coronary angiography-based end points of coronary artery disease progression predict clinical coronary events. Subjects who demonstrate greater coronary artery lesion progression have an increased risk of future clinical coronary events. Design of shorter, smaller trials of antiatherosclerotic agents is justified.

Complications and prognostic factors in Vogt-Koyanagi-Harada disease☆

PURPOSE To identify associations between complications of disease and final visual acuity in patients with Vogt-Koyanagi-Harada disease and to identify prognostic factors for disease outcome. METHODS All patients diagnosed with Vogt-Koyanagi-Harada disease at the Doheny Eye Institute or the Los Angeles County/University of Southern California Medical Center between 1983 and 1997 were reviewed. Data extracted included initial and final visual acuities, age, gender, ethnicity, complications, treatment, duration of disease, and number of recurrences. RESULTS One hundred one patients with Vogt-Koyanagi-Harada disease were identified, 68 (67%) of which were female. Mean age was 34 +/- 14 years (range, 8 to 75 years). Asians presented at a significantly older age than all other groups. One hundred three eyes (51%) developed at least one complication, including cataract in 84 eyes (42%), glaucoma in 54 eyes (27%), choroidal neovascular membranes in 22 eyes (11%), and subretinal fibrosis in 13 eyes (6%). Patients who developed at least one complication had a significantly longer median duration of disease and number of recurrent episodes of inflammation (P =.0001 for each) than did those patients who developed no complications. Statistically significant associations existed between poor final visual acuity and greater numbers of complications (P =.001), greater age at onset (P =.03), a longer median duration of disease (P =.03), and greater number of recurrent episodes of inflammation (P =.0004). Eyes possessing a better visual acuity at presentation were more likely to have a better visual acuity at final follow-up (P =.001). CONCLUSIONS Factors associated with a worse final acuity included increasing numbers of complications, greater age at onset, and worse acuity at presentation.

Post-traumatic proliferative vitreoretinopathy. The epidemiologic profile, onset, risk factors, and visual outcome

PURPOSE The purpose of the study was to characterize the clinical development of proliferative vitreoretinopathy (PVR) after trauma in the human eye. METHODS A chart review was performed on the records of 1564 patients with ocular trauma seen at a large metropolitan hospital. The frequency, type of ocular trauma, time to onset, potential risk factors, and visual outcome for PVR were evaluated. RESULTS Proliferative vitreoretinopathy occurred in 71 (4%) of 1654 injured eyes. Of these 71 injured eyes, 30 (42%) resulted from rupture, 15 (21%) from penetration, 13 (18%) from perforation, and 7 (10%) from confusion. Six (9%) were associated with an intraocular foreign body (IOFB). The frequency of PVR following perforation, rupture, penetration, IOFB, and contusion was 43%, 21%, 15%, 11%, and 1%, respectively. Overall, those eyes that developed PVR had a poorer visual outcome, with PVR being the primary reason for visual loss. The time from injury to onset of PVR was shortest after perforation (median, 1.3 months), followed by rupture (2.1 months), IOFB (3.1 months), penetration (3.2 months), and contusion (5.7 months). Vitreous hemorrhage was the strongest independent predictive factor for the development of PVR. A long, posteriorly located wound and persistent intraocular inflammation were also important risk factors for PVR. CONCLUSIONS These results suggest that PVR is a common complication following a variety of ocular injuries, and that it is associated with a poor visual outcome. Its frequency, onset, and outcome are strongly dependent on the nature of the trauma. Specific high-risk groups are identified as candidates for more aggressive therapy.

Intermediate-term Results of a Randomized Clinical Trial of the 350- versus- the 500-mm2 Baerveldt Implant

BACKGROUND The Baerveldt glaucoma implant is a large equatorial aqueous shunting device that is installed through a single-quadrant conjunctival incision. The intermediate-term results of a randomized study comparing the 350- and 500-mm2 Baerveldt implants are reported. METHODS Seventy-three patients with medically uncontrollable, nonneovascular glaucomas associated with aphakia, pseudophakia, or failed filters were enrolled in a randomized, prospective study comparing 350- and 500-mm2 Baerveldt implants. Surgical success was defined as 6 mmHg < or = final intraocular pressure < or = 21 mmHg without glaucoma reoperation or devastating complication. RESULTS Of patients with 350- and 500-mm2 implants, 93% and 88%, respectively, achieved surgical success (18-month life-table analysis, P = 0.93). The 500-mm2 implants afforded intraocular pressure control with significantly fewer medications (0.7 versus 1.3; P = 0.006). The postoperative visual acuities remained within one line of the preoperative visual acuities or improved in 62% and 66% of patients in the 350- and 500-mm2 groups, respectively (P = 0.93). Complication rates were statistically similar. The most frequent ones in the 350- and 500-mm2 groups, respectively, were serous choroidal effusion (16% and 32%), strabismus (16% and 19%), anterior uveitis (14% and 11%), and corneal or corneal graft edema (11% each). CONCLUSION The intermediate-term results of the 350- and 500-mm2 Baerveldt implants were statistically comparable with respect to surgical and visual outcomes, as well as complications, although the larger implant was associated with a higher rate of some complications. However, the 500-mm2 Baerveldt implant afforded intraocular pressure control with fewer medications than the 350-mm2 implant.