Factors associated with variability in retinal nerve fiber layer thickness measurements obtained by optical coherence tomography.

OBJECTIVE: To identify factors associated with variability in retinal nerve fiber layer (RNFL) thickness measurements obtained by optical coherence tomography (OCT). DESIGN: Retrospective observational case series. PARTICIPANTS: One hundred fifty consecutive patients with known or suspected glaucomatous optic nerve damage undergoing OCT imaging for RNFL thickness measurement. METHODS: One eye with known or suspected glaucoma from each patient was scanned twice within the same visit using the Stratus OCT's fast nerve fiber layer thickness acquisition protocol. For each scan, the average RNFL thickness, signal strength (a measure of the amount of light reflecting back from the retina), and analysis confidence (AC, a measure of the quality of the data as reported by the OCT software) were recorded. Retinal nerve fiber layer thickness measurements of the initial and repeat scans for each case were compared, and the difference in thickness measurements was correlated with difference in signal strength, AC (either low or normal), and the average RNFL thickness. MAIN OUTCOME MEASURE: Difference in RNFL thickness. RESULTS: The mean difference in RNFL thickness between the initial and repeat scans was 10 microns (12.5%; range, 0.04-86.15 microns). Difference in signal strength between initial and repeat scans positively correlated with the difference in RNFL thickness (Spearman correlation coefficient = 0.44; P<0.001), whereas the average nerve fiber layer thickness negatively correlated with the difference in RNFL thickness (Spearman correlation coefficient = -0.25; P = 0.002). The presence of a scan with low AC was associated with a lower average RNFL thickness and a greater difference in RNFL thickness between the initial and repeat scans. CONCLUSIONS: Signal strength variability, low AC, and low RNFL thickness are associated with variability in RNFL thickness measurements obtained by Stratus OCT. Comparability of RNFL thickness measurements between visits may be improved if scans of similar signal strengths without low AC are obtained. This is especially important for patients with moderate glaucomatous optic nerve damage and for patients from whom good quality scans are not obtainable.

Intravitreal triamcinolone acetonide for the treatment of immune recovery uveitis macular edema.

PURPOSE: To evaluate the use of intravitreal triamcinolone (IVTA) for the treatment of macular edema secondary to immune recovery uveitis (IRU) in patients with AIDS. DESIGN: Prospective, consecutive, interventional case series. PARTICIPANTS: Eight eyes of 7 patients receiving 13 injections. METHODS: Prospective, consecutive, interventional case series of 13 injections involving 8 eyes in 7 patients who underwent an intravitreal injection of 20 mg decanted triamcinolone acetate for fluorescein angiographically proven IRU-related macular edema. MAIN OUTCOME MEASURES: The primary outcome measure was vision (using the Early Treatment Diabetic Retinopathy Study chart). Other outcome measures included fluorescein angiography and optical coherence tomography. RESULTS: Visual acuity improved at all time points and was statistically significant at the 1-month and 3-month follow-up examinations. The average visual improvement was 3 lines at 3 months. Retinal volume and thickness improvement were statistically significant at all time points. All patients had a minimum follow-up of 9 months, and there were no cases of cytomegalovirus reactivation. CONCLUSIONS: Previous studies showed that treatment with sub-Tenon repository steroids for the treatment of macular edema of IRU was only marginally effective. However, the current study shows that IVTA can be an effective short-term treatment for macular edema secondary to IRU in patients with AIDS. Longer follow-up is needed to assess the durability of the effect and to monitor for longer-term complications and outcomes.

Differences in clinical findings between Caucasians and African Americans with biopsy-proven sarcoidosis.

OBJECTIVE: To study the prevalence of ocular manifestations in African American and Caucasian patients with biopsy-proven sarcoidosis at the initial ophthalmic examination and to determine the relationship between angiotensin-converting enzyme (ACE) levels, chest x-ray findings, and ocular signs of sarcoidosis. DESIGN: Retrospective, cross-sectional, observational study. PARTICIPANTS: Eighty-one consecutive patients with biopsy-proven sarcoidosis seen at the Doheny Eye Institute from January 1989 through April 2005. METHODS: Medical records were reviewed to obtain demographic data, biopsy site, initial ocular findings, pulmonary symptoms, and results of serum ACE levels and chest x-rays. Associations between ACE level/chest x-ray stages and ocular manifestations related to sarcoidosis were obtained from these data. MAIN OUTCOME MEASURES: Ocular manifestations related to sarcoidosis. RESULTS: Of the 81 patients, 35 were Caucasian; 29 were African American; and the remaining 17 were Hispanic, Asian Indian, and other races. Female patients were older than males (P = 0.05). Sixty-five (80%) of the 81 patients had ocular manifestations related to sarcoidosis. Thirty-three patients (40.7%) had uveitis, 12 (14.8%) had adnexal granulomas, and 25 (30.8%) had keratoconjunctivitis sicca. Of the 33 patients with uveitis, 22 presented with nongranulomatous inflammation. There was no significant association between ocular manifestations related to sarcoidosis and serum ACE levels (P = 0.43) or chest x-ray stage (P>0.99). Of the 29 African American patients, 26 (89.7%) had ocular manifestations related to sarcoidosis, compared with 24 (68.6%) of the 35 Caucasians (P = 0.12). The African American patients were younger (mean age, 44.4 years) than the Caucasian patients (mean age, 52.0) (P = 0.003) and had higher mean ACE levels (P = 0.003). A significantly high proportion of African American males presented with uveitis (P = 0.005), and a significantly high proportion of African American females presented with adnexal granulomas (P = 0.05). CONCLUSIONS: The present study reveals that patients with sarcoidosis can present initially with clinical features of nongranulomatous uveitis. Relative to Caucasians, African American patients with sarcoidosis tend to be younger when they first present to the ophthalmologist and to present with uveitis and/or adnexal granuloma. Serum ACE levels and chest x-ray stages may not help predict the occurrence of ocular changes in sarcoidosis.

Assessment of retinal function in patients with HIV without infectious retinitis by multifocal electroretinogram and automated perimetry.

PURPOSE: To determine if multifocal electroretinogram (mfERG) testing shows abnormalities that correspond to perimetric defects in HIV positive patients without infectious retinitis. METHODS: We studied three groups of patients: HIV negative controls, HIV high CD4 nadir patients (lowest CD4 T cell count is over 100) and low CD4 nadir patients (below 100 for over 6 months). Twenty-six HIV positive eyes and 16 HIV negative control eyes were studied by mfERG. A subset of 10 eyes also underwent computerized perimetry for comparison. We analyzed mfERG by hexagons as well as by quadrants and rings. RESULTS: Of 103 hexagon locations there was no significant difference in the amplitudes P1 and N1 (nV/degree) between the three studied groups (p>0.05), similarly, the latencies were not different (p>0.05). All eyes with significant visual field defects at the 0.01 and 0.005 level (Humphrey pattern deviation; 24-2) were compared to mfERG amplitudes and latencies at those locations-there were no corresponding defects in mfERG data (p>0.2). CONCLUSION: In the era of HAART there are still demonstrable visual field defects and other evidence of damage to the retinal nerve fiber layer in HIV patients. Our mfERG studies show that the damage appears to affect the inner retina, the outer retina is spared. Further studies of inner retinal structure and function are indicated to elucidate this process.

Esterified estrogens combined with methyltestosterone raise intraocular pressure in postmenopausal women.

PURPOSE: To investigate the effect of esterified estrogens combined with methyltestosterone (EECM) (Estratest, Solvay, Pharmaceuticals, Inc, Baudette, Minnesota, USA) on intraocular pressure (IOP) in postmenopausal women. DESIGN: Observational case series. METHODS: The IOP of 13 consecutive postmenopausal women with dry eye syndrome were recorded before and during EECM therapy (1.25 mg of esterified estrogens and 2.5 mg of methyltestosterone for several months). RESULTS: The mean IOP increased from a baseline of 15.0 mm Hg before treatment to 18.2 mm Hg on EECM therapy (P < .0001) after a median duration of 11.3 months (range, 0.9 to 24 months). The increase in IOP was statistically significant at the 0.05 level of significance within three months and continued over 12 months. Two patients whose pressures increased (>4 mm Hg) returned to baseline levels after EECM was discontinued. CONCLUSIONS: Esterified estrogens combined with methyltestosterone produce a clinically significant increase in IOP in postmenopausal women with dry eye syndrome.

Photodynamic therapy for choroidal neovascularisation secondary to inflammatory chorioretinal disease.

INTRODUCTION: To review the long-term outcome of photodynamic therapy (PDT) with verteporfin for inflammatory chorioretinal disease with subfoveal choroidal neovascularisation (CNV) over a 1-year period. MATERIALS AND METHODS: Retrospective review of eyes with subfoveal CNV for associated choroiditis that were treated with PDT using verteporfin over a 1-year period. MAIN OUTCOME MEASURE: visual acuity. RESULTS: Five eyes in 4 patients, with diagnoses including serpiginous choroiditis (2), ocular histoplasmosis syndrome (OHS, 1), and punctate inner choroidopathy (PIC, 2) underwent standard treatment procedure for PDT with verteporfin. Visual acuity, fluorescein angiography and treatment parameters were reviewed. Follow-up ranged from 12 months to 36 months (median, 36 months). Pre-PDT visual acuities ranged from 20/60 to 20/400 (median, 20/200). Post-PDT visual acuities ranged from 20/30 to 20/400 at 1 year (median, 20/300). Visual acuity was stabilised (within 1 line) or improved (greater than 1 line) in 3 eyes at 1 year and 4 of the 5 eyes at last follow-up. CONCLUSION: PDT for subfoveal CNV may stabilise, but rarely improves, visual acuity in eyes with choroidal neovascularisation secondary to inflammatory chorioretinal disease.

Long-term study of intraocular pressure changes in patients with human immunodeficiency virus treated with highly active antiretroviral therapy.

PURPOSE: To characterize a longitudinal relationship between highly active antiretroviral therapy immune recovery as defined by an increase in CD4 cell counts and any associated changes in intraocular pressure (IOP) in both patients with and patients without a history of cytomegalovirus (CMV) retinitis and to determine if human immunodeficiency (HIV)-induced reduction in IOP is reversible. DESIGN: Retrospective analysis of patient data collected from 1997 through 2004. PARTICIPANTS: Cohort of patients from one eye center, including patients from the Longitudinal Study of Ocular Complications of Acquired Immunodeficiency Syndrome. METHODS: Linear regression analyses were conducted within the CMV and non-CMV groups to determine the change in IOP per 100-unit change in CD4 count. Average changes in IOP per change in CD4 count were compared between the CMV and the non-CMV groups using a Wilcoxon rank-sum test. Linear regression analyses were conducted within the CMV and non-CMV groups to determine the linear relationship between the 12-month change in IOP per 12-month 100-unit change in CD4 count. MAIN OUTCOME MEASURE: Intraocular pressure in relation to changes in CD4 cell counts. RESULTS: Compared with the non-CMV group, the median IOP change per change in CD4 count was not statistically different from the CMV group (0.9 vs. 1.7 mmHg/100 CD4 cells, respectively; P = 0.20). Analysis of the linear relationship between the 12-month change in IOP and the 12-month change in CD4 count within both the CMV and non-CMV groups showed a strong linear relationship: 67% of the variability in a 12-month IOP change for the CMV group (P<0.0001) and 36% of the variability in a 12-month IOP change for the non-CMV group (P<0.001). CONCLUSIONS: Reduction in T-lymphocyte count in HIV infection is accompanied by a decrease in IOP in both CMV-infected and non-CMV-infected eyes, and immune recovery is associated with an increase in IOP.

One-year results of a pilot study using oral 13-cis retinoic acid as a treatment for subfoveal predominantly occult choroidal neovascularization in patients with age-related macular degeneration.

PURPOSE: To evaluate the safety and evidence of efficacy for oral 13-cis retinoic acid as a treatment for patients with subfoveal occult choroidal neovascularization (CNV) due to age-related macular degeneration (ARMD). METHODS: Patients with active, subfoveal occult CNV with no prior treatment of the subfoveal component were eligible for inclusion. Patients received 40 mg of 13-cis retinoic acid twice daily for 5 months, stopped treatment for 2 months, and then resumed treatment for 5 months. Patients were observed monthly with Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity (VA), clinical examination, fluorescein angiography, and laboratory testing. RESULTS: Eleven patients, aged 64 to 88 years, were enrolled and followed for 1 year. Initial VA ranged from 55 (20/40) to 5 (20/400) ETDRS letters (median 48 letters). Mild drug-related side effects (dry skin, chapped lips) occurred in all 11 patients. Three patients experienced more severe side effects (muscle aches, mood swings) and did not resume treatment after the drug holiday. Moderate VA loss occurred in 36% at both 6 and 12 months. CONCLUSIONS: Oral 13-cis retinoic acid is too toxic to be useful in patients with ARMD. Oral 13-cis retinoic acid did not improve vision although it may have slowed visual acuity loss in patients with ARMD with occult subfoveal CNV.

Effect of a novel octapeptide urokinase fragment, A6, on experimental choroidal neovascularization in the monkey.

PURPOSE: To evaluate the inhibitory effects of a urokinase-derived octapeptide, A 6, on laser-induced choroidal neovascularization (CNV) in monkeys. METHODS: Twenty female cynomolgus monkeys were randomly grouped into weekly or monthly A 6 treatment groups, each consisting of 10 animals. CNV was induced in both eyes by perimacular laser treatment. In each right eye, a single 22.25-mg A 6 dose (monthly group) or 4 22.25-mg A 6 doses each week (weekly group) were given by intravitreal injections. Each left eye received phosphate buffer on the same schedule. Monkeys were observed for 4 weeks by ophthalmic examinations, color photography, and fluorescein angiography. RESULTS: Weekly treated eyes had a 35% reduction of CNV compared with controls (P = 0.23). In contrast, monthly treated eye had a 71% reduction of CNV compared with controls (P = 0.0009). There was no evidence of toxicity at both clinical and pathologic examinations. CONCLUSIONS: Intravitreal A 6 injections effectively inhibited CNV in cynomolgus monkeys without evidence of toxicity. The overall reduction in CNV was greater for monthly treated eyes than for weekly treated eyes. This study suggests that A 6 has promise as a local antiangiogenic treatment of CNV. Further work is indicated to evaluate the potential role of A 6 in therapy for human CNV associated with age-related macular degeneration.

Errors in retinal thickness measurements obtained by optical coherence tomography.

OBJECTIVE: To report the frequency and severity of optical coherence tomography (OCT) retinal thickness measurement errors and to describe parameters that predict these errors. DESIGN: Observational case series. PARTICIPANTS: Two hundred consecutive patients undergoing OCT imaging. METHODS: One eye (primary) from each of 200 consecutive patients undergoing Stratus OCT imaging (Carl Zeiss Meditec, Dublin, CA) with radial lines or fast macular thickness-based acquisition protocols was selected for review by 2 graders. On each of the line scans, graders evaluated the position of the automated retinal boundary lines (inner retinal surface and retinal pigment epithelium band) used by the OCT machine for thickness calculations and graded the positioning on a 6-point subjective, categorical error scale to generate an error score. The presence of thickness errors was correlated with various parameters, including the analysis confidence assessment reported by the OCT software, disease diagnosis, retinal morphologic features, the foveal center thickness standard deviation (FCTSD), and the FCTSD-to-foveal center thickness (FCT) ratio. MAIN OUTCOME MEASURE: Average OCT retinal thickness error score. RESULTS: Errors of retinal boundary detection and thickness measurement were observed in 92% of eyes, but were severe in only 13.5% of eyes. The identification of an error or low analysis confidence by the OCT software was strongly associated with the severity of the retinal thickness errors. A higher FCTSD-to-FCT ratio and presence of subretinal fluid also were associated with more severe errors. Retinal cysts and a diagnosis of retinal vascular disease such as diabetic macular edema were less likely to be associated with significant errors. CONCLUSIONS: Retinal thickness measurement errors occur frequently with current OCT segmentation and analysis algorithms. Severe errors are more frequent in eyes with subretinal pathologic features, but generally are detected by the OCT software. A high FCTSD-to-FCT ratio (>0.1) also may alert the clinician to the possibility of thickness errors. Clinical studies, particularly those pertaining to subretinal diseases, should consider these errors when incorporating OCT imaging in the study design.

Implantation of an inactive epiretinal poly(dimethyl siloxane) electrode array in dogs.

The aim of this study is to investigate the long-term, mechanical biocompatibility of a polymer microtechnology that can be used to position electrodes in close proximity to the retina. Poly(dimethylsiloxane) (PDMS) arrays were manufactured by soft-lithography at Lawrence Livermore National Laboratory. The PDMS implant measured 4 mm x 40 mm x 55-60 microm and included 4-8 electrodes. Micromolded ribs were placed at the perimetry for strength and ease of manipulation. The PDMS arrays were implanted epiretinally in four normal dogs, with a single retinal tack used in each case to hold the device on the retina. The mechanical effects of the implant were followed up after surgical implantation by photography, fluorescein angiography, optical coherence tomography (OCT), and electrophysiologic tests. An intraoperative retinal tear occurred in the first implanted dog, causing retinal detachment and necessitating termination. The remaining dogs experienced no gross complications secondary to the array implantation procedure. During the follow-up period of 2 months in one eye and 6 months in three eyes, OCT demonstrated that the arrays were in close contact with the retina. Fluorescein angiography showed good perfusion of the retina under the array. At the end of 6 months, there was no statistical difference from baseline in mean retinal thickness under the array (P=0.43) or peripapillary retinal nerve fibre layer thickness corresponding to the implanted area (P=0.34). The mean distance between the array and the retinal surface varied from 32 to 68 microm throughout the follow-up. Histopathologic evaluation of the retinal implantation site in eyes followed for 6 months showed a general preservation of the normal, layered retinal structure, except for some localized retinal thinning in two eyes, where the array frame had been in direct retinal contact. The PDMS substrate micro array is a new and promising technology that can be scaled to support a high-density retinal stimulating array. Its implantation and handling is surgically manageable, and it forms a mechanically stable, acceptable interface with the inner retinal surface.

Results of silicone oil removal in patients with cytomegalovirus retinitis related retinal detachments.

PURPOSE: To evaluate the percentage and risk indicators leading to retinal redetachment in HIV (human immunodeficiency virus) patients with CMV (cytomegalovirus) retinitis related retinal detachments that were repaired with silicone oil, and then subsequently underwent oil removal. DESIGN: Retrospective, noncomparative interventional case series. METHODS: The study cohort consisted of a series of 15 eyes in 14 patients with HIV and CMV retinitis with a retinal detachment (RD) repaired with silicone oil at a single center and followed from the time of the CMV retinitis diagnosis through the time of silicone oil removal. Patient- and eye-specific data regarding demographic and clinical characteristics were collected retrospectively and statistical analyses were performed to compare differences between the eyes that had retinal detachments versus the eyes that remained attached following removal of silicone oil. RESULTS: Eight eyes (53%) redetached after a median of 4.0 months following oil removal. Cataract surgery performed at the time of oil removal was a statistically significant risk factor for redetachment (P = .01). There was a trend for lower CD4 levels to be associated with a higher risk of retinal redetachment. The use of a scleral buckle at the time of surgery (initial RD repair or at the time of oil removal) did not reduce the risk of redetachment. CONCLUSIONS: Approximately half of the eyes with CMV related retinal detachment may safely undergo oil removal. The risk factor for redetachment was simultaneous cataract extraction at the time of silicone oil removal. There was also a trend for lower CD4 levels to be associated with a higher risk of retinal redetachment.

Intraoperative optical refractive biometry for intraocular lens power estimation without axial length and keratometry measurements.

PURPOSE: To correlate intraoperative aphakic autorefraction to conventional emmetropic intraocular lens (IOL) calculations and derive an empiric predictive model for IOL estimation based on optical refractive biometry without axial length and keratometry measurements. SETTING: Institutional Review Board of the University of Southern California, Los Angeles County General Hospital, Los Angeles, California, USA. METHODS: A pilot group of 22 eyes of 22 patients scheduled for cataract surgery were enrolled in a prospective trial. All patients had a standard preoperative workup with subsequent cataract extraction and IOL implantation according to conventional biometric measurements and IOL calculations. Intraoperative autorefractive retinoscopy was used to obtain aphakic autorefraction and to measure the aphakic spherical equivalent before lens implantation. A linear regression analysis was used to correlate the aphakic spherical equivalent to the final adjusted emmetropic IOL power to empirically derive a refractive formula for IOL calculation (optical refractive biometry method). A second validation series of 16 eyes was used in a head-to-head comparison between the optical refractive biometry and the conventional IOL formulas. A subset of 6 eyes from the validation series were post-refractive cases having subsequent cataract surgery. RESULTS: Intraoperative retinoscopic autorefraction was successfully obtained in all 22 patients in the pilot group and all 16 patients in the validation group. The spherical equivalent of the aphakic autorefraction correlated linearly with the final adjusted emmetropic IOL power (P<.0001, with adjusted r(2)=.9985). The relationship was sustained over an axial length range of 21.43 to 25.25 mm and an IOL power range of 12.0 to 25.5 diopters (D). In a subsequent validation series of 10 standard and 6 post-laser in situ keratomileusis (LASIK) cataract cases, the optical refractive biometry method proved to be a better predictive model for IOL estimation than conventional formulas; 83% of the LASIK eyes and 100% of the normal eyes were within +/-1.0 D of the final IOL power when aphakic autorefraction was used, compared with 67% of LASIK eyes and 100% of the normal eyes, using the conventional methodology. CONCLUSIONS: A new model for IOL power calculation was derived based on an optical refractive methodology that breaks away from the conventional art introduced by Fyodorov in the 1960s. A purely refractive algorithm is used to predict the power of the IOL at the time of surgery without the need for axial length and keratometry measurements. This method bypasses some limitations of conventional biometry and shows promise in the post-refractive cataract cases.

Long-term stimulation by active epiretinal implants in normal and RCD1 dogs.

An epiretinal prosthesis, consisting of an extraocular microelectronic stimulator and an intraocular electrode array, was implanted in one eye of three blind and three sighted dogs. Three dogs (2 blind, 1 normal) were stimulated for 120 days, and two dogs (both normal) for 60 and 103 days respectively for 8-10 h/day at levels of 0.1 mC cm(-2) and 0.05 mC cm(-2), with each stimulus level presented to half of the array. One blind dog was kept as an inactive implant control. During the study period, electroretinograms (ERG) and fundus photographs were recorded. At the end of the study period, the dogs were sacrificed and histological and morphometric evaluation was made of the retina. No inflammatory reaction, neovascularization or hemorrhage was observed during the follow-up examinations. ERGs were unchanged. Stimulus levels used were of sufficient amplitude to elicit cortical evoked potentials. Histological evaluation showed no inflammatory infiltrates or changes in retina morphometry related to electrical stimulation when compared to the unstimulated control eye. Morphometric analysis revealed no consistent differences relating to electrical stimulation. In summary, chronic electrical stimulation of the dog retina at up to 0.1 mC cm(-2) with an epiretinal prosthesis does not appear to adversely affect the retina.

Experience with the baerveldt glaucoma implant in the management of pediatric glaucoma.

PURPOSE: To report the clinical outcome in 48 eyes of 48 children who received a Baerveldt glaucoma implant (BGI) for the management of pediatric glaucoma. DESIGN: Retrospective, noncomparative case series. METHODS: The medical records of all patients with pediatric glaucoma who underwent a BGI at two tertiary care referral centers in Los Angeles between 1990 and 1999 were reviewed. Intraocular pressure (IOP), intraoperative and postoperative complications, number of glaucoma medications, visual acuity, and pre- and postoperative corneal diameter and axial length were collected from patient records. Criteria for success were IOP between 6 and 21 mm Hg with or without glaucoma medications, no need for further glaucoma surgery, the absence of visually threatening complications, and some residual vision (minimum visual acuity of light perception). RESULTS: The study included 48 eyes from 48 patients aged 16 years and younger (mean age 4.1 years). Mean preoperative IOP was 31.2 +/- 25.7 mm Hg, and mean postoperative IOP was 16.4 +/- 4.9 mm Hg. Cumulative probability of success (based on the Kaplan-Meier survival curve) was 95% at 6 months, 90% at 1 year, 84% at 2 years, 74% at 36 months, and 58% at 48 months. On average, the BGIs were successful for a mean period of 5.6 years (67.7 months). Overall, 11 eyes failed, with the causes being uncontrolled IOP (eight eyes), retinal detachment (two eyes), and no light perception (one eye). CONCLUSIONS: Baerveldt glaucoma implants can be a safe and effective treatment modality for the management of pediatric glaucoma refractive to medical therapy.

Race-ethnic differences in the extent, prevalence, and progression of coronary calcium.

OBJECTIVE: To compare across four race-ethnic groups the baseline prevalence and extent of coronary calcium and the 7-year rate of progression in the extent of coronary calcium. DESIGN: The South Bay Heart Watch is a prospective cohort study designed to appraise the value of coronary calcium for predicting cardiovascular outcomes in asymptomatic adults with cardiac risk factors. Statistical analyses were conducted to evaluate ethnic differences in the prevalence, extent, and progression of coronary calcium among Caucasian, African-American, Hispanic, and Asian participants. SETTING: Population-based study. PATIENTS OR PARTICIPANTS: Between December 1990 and December 1992, 1289 participants without coronary heart disease underwent baseline risk factor screening and computed tomography for coronary calcification (Cohort 1). Seven years later, 828 (64%) participants returned for follow-up evaluation and re-scanning (Cohort 2). MAIN OUTCOME MEASURES: Prevalence, extent, and progression of coronary artery calcium. RESULTS: In Cohort 2, compared to Whites, African Americans had a lower prevalence of coronary calcium at baseline (P=.012) and follow-up (P=.005), smaller calcium scores at baseline (P=.005) and follow-up (P=.0004), and less progression (P=.001); Hispanics had a lower prevalence of coronary calcium at follow-up (P=.04) with smaller calcium scores (P=.011), and less progression (P=.009). In contrast, no differences were seen between Whites and Asian/Pacific Islanders. Race-ethnic differences in progression persisted after adjusting for risk factors and participation bias (P<.05). CONCLUSIONS: The present results lend further credence to the notion that race-ethnic differences exist in the prevalence and rate of progression of coronary calcification. The relationship between calcification and the incidence of coronary heart disease in these race-ethnic groups needs further exploration.

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 microm 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 microg/m3 (mean, 20.3). For a cross-sectional exposure contrast of 10 microg/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 (greater than or equal to 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.

Relation of coronary calcium progression and control of lipids according to National Cholesterol Education Program guidelines.

Tracking of coronary artery calcium (CAC) has been suggested for monitoring the effects of lipid control, but it is not known whether lipid control decreases progression of CAC. Seven hundred sixty-one subjects (mean age 64.5 +/- 7.3 years; 91% men; 69% positive for CAC) in an ongoing cohort study underwent baseline and follow-up (after 7.0 +/- 0.5 years) computed tomography for CAC. Subjects were stratified into low-risk (<2 risk factors), intermediate-risk (> or =2 risk factors but <20% risk of coronary heart disease over 10 years), or high-risk (> or =2 risk factors and >20% risk of coronary heart disease in 10 years or diabetes) groups. Lipid control was defined according to criteria of the National Cholesterol Education Program. Two-way analysis of covariance was used to examine the relation of low-density lipoprotein (LDL) cholesterol and risk group to change in CAC volume score. Control of levels of high-density lipoprotein (HDL) cholesterol and triglycerides was also examined in relation to progression of CAC. After adjustment for other risk factors and baseline CAC volume, CAC progression was similar between those with adequate and those with inadequate control of LDL cholesterol (p = 0.68) and across categories of optimal, intermediate, and higher risk LDL cholesterol (p = 0.40). However, higher levels of HDL cholesterol (> or =1.5 mmol/L [60 mg/dl]) were associated with less progression of CAC volume (151 vs 203 mm(3) in those with HDL cholesterol <1.0 mmol/L [40 mg/dl], p = 0.03). There was no relation between triglycerides and CAC progression (p = 0.54). Our findings do not support the use of CAC assessment for monitoring the control of LDL cholesterol, but greater progression of CAC may occur in those in whom HDL cholesterol is not controlled.

Prophylactic effect of IL-10 gene transfer on induced autoimmune dacryoadenitis.

PURPOSE: To evaluate the effect of viral IL-10 on the lacrimal gland immunopathologic response in the ocular surface disease, induced autoimmune dacryoadenitis. METHODS: Disease was induced in rabbits by injecting inferior lacrimal glands with peripheral blood lymphocytes activated by 5 days of coculture with autologous acinar cells in a mixed-cell reaction. In the treated group, an adenoviral vector carrying the vIL-10 gene was concurrently injected with activated lymphocytes. Tears were collected periodically for quantitation of IL-10 by ELISA. Two weeks after disease induction, tear production, tear film breakup time, and rose bengal staining score were determined. Sectioned glands were immunostained for expression of CD4, CD8, rabbit thymic lymphocyte antigen (RTLA), CD18 and major histocompatibility complex class II. RESULTS: The titer of vIL-10 in tears was at its maximum on day 3, started to decline by day 7, and was undetectable by day 14. In the diseased group, the tear production rate and tear film breakup time were significantly decreased, and rose bengal staining was significantly increased. Diseased glands had immune cell infiltrates containing CD4+, RTLA+, and CD18+ cells, and major histocompatibility complex class II expression was increased. These changes were significantly ameliorated by expression of vIL-10. CONCLUSIONS: In vivo transduction of the lacrimal gland with AdvIL-10 resulted in the transient appearance of vIL-10 in tears. The presence of vIL-10 partially suppressed the appearance of Sjögren-syndrome-like features of reduced tear production, accelerated tear breakup, ocular surface disease, and immunopathologic response. Anti-inflammatory cytokine gene expression may offer a therapeutic modality for the treatment of autoimmune dacryoadenitis, once suitable vectors become available.

Valganciclovir therapy for immune recovery uveitis complicated by macular edema.

PURPOSE: To determine whether treatment with valganciclovir will improve visual acuity in eyes with immune recovery uveitis complicated by macular edema. DESIGN: Prospective open label controlled Phase II drug study. METHODS: Five patients with chronic macular edema as a result of immune recovery uveitis were studied. Baseline fluorescein angiograms, best-corrected ETDRS visions, and cytomegalovirus (CMV) lymphoproliferative T-cell function assays were obtained and repeated after three months of valganciclovir therapy (900 mg daily) and again three months after withdrawal of therapy. RESULTS: Vision improved by a mean of 11 letters in the treatment phase (P =.05). Graded angiograms showed three patients had treatment reduction of macular edema. One patient had rebound increase in macular edema after the withdrawal phase. The CMV lymphoproliferative response was not affected by the valganciclovir. CONCLUSION: Results suggest valganciclovir treatment may benefit visual acuity in patients with macular edema from immune recovery uveitis.