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OBJECTIVE: To evaluate the performance of the BBL MGIT (Mycobacterial Growth Indicator Tube) AST SIRE system for the antimycobacterial susceptibility testing of Mycobacterium tuberculosis to isoniazid (at a concentration equivalent to the lower concentration used for testing by the method of proportion), rifampin, ethambutol, and streptomycin. DESIGN: Thirty-one clinical isolates and 30 challenge strains provided by the Centers for Disease Control and Prevention (CDC) were tested by MGIT AST SIRE using 2 methods of inoculum preparation, and results were compared with those of the method of proportion, which was considered the reference method. Clinical isolates for which the results of the 2 methods were discordant also were tested at 2 reference laboratories. RESULTS: Based on data from our site and the reference laboratories, agreement rates between initial MGIT AST SIRE results and the method of proportion for the clinical isolates with the inoculum prepared from a McFarland equivalent and from a positive MGIT tube, respectively, were 100% and 96.8% for isoniazid, 100% and 100% for rifampin, 96.8% and 100% for ethambutol, and 100% and 100% for streptomycin, excluding the isolate for which the discordant streptomycin result could not be resolved. For the 30 challenge isolates, agreement rates between MGIT AST SIRE and expected results and between method of proportion and expected results, respectively, were 96.7% and 93.3% for isoniazid, 93.3% and 100% for rifampin, 83. 3% and 100% for ethambutol, and 93.3% and 100% for streptomycin. For the clinical isolates, the mean time to an MGIT AST SIRE result of susceptible was 6.15 +/- 0.13 days (range, 5-8 days). For a result of resistant, the mean time overall was 5.00 +/- 0.24 days (range, 3-8 days). CONCLUSION: These data suggest that the MGIT AST SIRE system, using either method of inoculum preparation, is an acceptable alternative to the BACTEC 460 TB method of susceptibility testing of clinical isolates of M tuberculosis to isoniazid, rifampin, ethambutol, and streptomycin. Reasons for the lower agreement with the CDC challenge isolates should be investigated. Further evaluation of the MGIT AST SIRE system using a concentration of isoniazid equivalent to the higher concentration tested by the method of proportion would be useful, because the decision concerning use of this agent generally is based on the susceptibility test result at the higher concentration.

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The reliability of the enhanced Amplified Mycobacterium Tuberculosis Direct Test (E-MTD; Gen-Probe, Inc., San Diego, Calif.) for rapid diagnosis of pulmonary tuberculosis (TB) was evaluated by testing 1, 004 respiratory specimens from 489 Texas prison inmates. Results were compared to those of mycobacterial culture (BACTEC TB 460 and Middlebrook 7H11 biplates), smear for acid-fast bacilli (AFB; auramine O), and clinical course. After chart review, three patients (nine specimens) who were on antituberculosis therapy before the study began were excluded from final analysis. Of the remaining 995 specimens, 21 were AFB smear positive: 13 grew Mycobacterium tuberculosis complex (MTBC), 6 grew nontuberculous mycobacteria, and 2 (from two patients diagnosed with TB and started on therapy after the study began) were culture negative. Twenty-eight specimens (20 patients) were positive for MTBC by culture and E-MTD. Seven specimens (seven patients) were positive by culture alone; three were from patients who had other E-MTD-positive specimens, two were false-positive cultures, and two were false-negative E-MTD results. Eight specimens were positive by E-MTD only; four specimens (four patients) were false-positive E-MTD results, and four specimens were from two patients with earlier E-MTD-positive specimens that grew MTBC. Thus, there were 22 patients with TB (10 smear positive and 12 smear negative). The sensitivity and specificity of the AFB smear for diagnosis of TB, by patient, were 45.5 and 98.9%, respectively. After resolving discrepancies, these same values for E-MTD were 90.9 and 99.1% overall, 100 and 100% for the smear-positive patients, and 83.3 and 99.1% for the smear-negative patients. Excluding the one smear-negative patient whose E-MTD-negative, MTBC culture-positive specimen contained inhibitory substances, the sensitivity of E-MTD was 95.2% overall and 90.9% in smear-negative patients. The specificity and positive predictive value of E-MTD can be improved, without altering other performance characteristics, by modifying the equivocal zone recommended by the manufacturer. These data suggest that E-MTD is a reliable method for rapid diagnosis of pulmonary TB, irrespective of the AFB smear result. Guidelines for the most appropriate use of E-MTD with smear-negative patients are needed.

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OBJECTIVE: To provide the first measures of the relative rates of rod and cone functional loss in patients with retinitis pigmentosa (RP) or cone-rod dystrophy (CRD). DESIGN: Five-year, prospective natural history study. PARTICIPANTS: Ninety-six patients (67 with RP and 29 with CRD) retaining measurable rod-mediated visual function and 5 normal subjects were tested at baseline and annually for 4 consecutive years. MAIN OUTCOME MEASURES: Tests of visual function included visual acuity, dark-adaptation thresholds, dark-adapted static perimetry, and rod and cone computer-averaged electroretinograms (ERGs), which were obtained over a range of retinal illuminances. Intervisit variability for each measure was obtained in a subset of patients who were tested twice within a 2-month interval and was used to determine whether an individual patient had shown progression, regression, or no change over a particular study interval. RESULTS: Over a 4-year interval, a significant number of patients with RP (60%) and CRD (62%) showed a decline in cone ERG amplitude. For rod ERG amplitude, the percentage of patients with RP or CRD showing progression was 64% and 45%, respectively. Although visual acuity, dark-adapted threshold, and rod visual field area also declined significantly over the 4-year period, the mean rate of change and the numbers of patients showing progression on these measures were lower than those for ERG measures. On specialized ERG testing, the yearly change in rod ERG threshold in RP was greater than the yearly change in cone ERG threshold, and the rate of progression varied significantly among inheritance types. For patients with CRD, the yearly change in rod threshold was comparable to the yearly change in cone ERG threshold. CONCLUSIONS: This study helps to define the natural progression of rod-mediated and cone-mediated functional loss in patients with RP and CRD.

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BACKGROUND: Active inflammation has not been traditionally associated with the ocular histoplasmosis syndrome. OBJECTIVE: To investigate the occurrence of presumed inflammatory chorioretinal lesions in patients with the ocular histoplasmosis syndrome. METHODS: Patients seen with acute symptoms and a clinical picture of ocular histoplasmosis were observed prospectively between August 13, 1993, and December 2, 1997. Symptoms, visual acuity, and fluorescein sodium angiography were used to document changes in inflammatory loci. RESULTS: Twelve patients were seen with active inflammatory lesions. Eleven had resolution of the loci with lessening of symptoms and improvement in acuity and angiographic findings. A typical subretinal neovascular membrane developed in 1 patient 8 months after the onset of symptoms. CONCLUSIONS: Inflammatory chorioretinal lesions can reactivate in the ocular histoplasmosis syndrome. In most of these patients, neovascularization did not develop and visual acuity was preserved.

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The reliability of the ESP Culture System II (ESP II; Difco Laboratories, Detroit, Mich.), a continuously monitoring mycobacterial culture system, was evaluated by comparing its performance with the BACTEC TB 460 (BACTEC TB) and Middlebrook 7H11/7H11 selective agar systems. A total of 2,283 specimens of all types (70.7% were respiratory specimens) were cultured; 149 (6.5%) yielded mycobacteria. The most common species recovered were Mycobacterium avium complex (MAC, 73 isolates) and Mycobacterium tuberculosis complex (MTBC, 53 isolates). The recovery rates by individual system were 87, 81, and 65% for ESP II, BACTEC TB, and Middlebrook agar, respectively, for all mycobacteria; the recovery rates were 89, 92, and 89%, respectively, for MTBC. For liquid plus solid medium system combinations, recovery rates for all mycobacteria and for MTBC, respectively, were 91 and 94% for ESP II plus Middlebrook agar and 85 and 96% for BACTEC TB plus Middlebrook agar. The difference between the recovery rates of all mycobacteria by ESP II and by BACTEC TB was not significant, whereas for the individual species, the only significant difference was recovery of more isolates of MAC by ESP II. For those isolates recovered in the individual systems, mean times to detection of all mycobacteria, MTBC, and MAC, respectively, were 13.1, 15.5, and 10.9 days for ESP II; 14.4, 16.6, and 12.1 days for BACTEC TB; and 17.8, 18.3, and 18.8 days for Middlebrook agar. ESP II is a reliable, nonradiometric, less labor-intensive alternative to BACTEC TB for growth and detection of mycobacteria, but as with other liquid culture methods, ESP II should be used in combination with a solid medium, not as a stand-alone system.

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Color matches were measured as a function of field diameter (1, 2, 4 and 8 deg) for 53 normal observers aged 13-80 yr. The difference between match midpoints for the 1 deg diameter and the other diameters decreased throughout adulthood, indicating an age-related change in optical density of cone outer segments in the central 1 deg. For all ages, there were large interobserver differences in the magnitude of the difference scores. These results provide an explanation for contradictions in the literature on the effects of age on cone optical density and on the magnitude of the color-match-area effect.

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Reduced foveal cone optical density in diseased eyes with normal acuity can affect color matches. Using field diameters of 1 degree, 2 degrees, 4 degrees, and 8 degrees, we measured mean color-match midpoints and match widths in patients who had good acuity and who exhibited three categories of eye disease: hereditary macular degeneration (n = 12), retinitis pigmentosa (n = 19), and glaucoma (n = 18). Results were compared with those for normal observers of comparable ages. Mean color-match midpoints were abnormal only for the population with hereditary macular degeneration, indicating a reduction in cone optical density in the central 4 degrees. Mean color-match widths were enlarged for both hereditary macular degeneration and retinitis pigmentosa, a result consistent with a reduction in the number of foveal cones.

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PURPOSE: To ablate retina and vitreous membranes using the 193-nm argon fluoride excimer laser in a fluid medium. METHODS: A special delivery system for the 193-nm excimer laser was developed that enabled the delivery of the laser into high-absorption liquid environments. The system was tested on the retina in an in vitro cup preparation of cow's eyes, and also in vivo on retina and vitreous membranes of rabbit eyes. The depth of cut as a function of laser energy was determined for an ablating needle with a 0.25-mm exit diameter. RESULTS: Gentle cutting of retinal tissue and of vitreous membranes was obtained in an energy range of 0.075 to 0.25 mJ/pulse. At the energy level of 0.075 mJ/pulse, four pulses were required for full-depth cut formation in rabbit retina, whereas at energy levels greater than 0.17 mJ/pulse, one pulse was sufficient for full-depth cut formation. The maximal rate of cutting achieved for the bovine retina was 2 mm/sec at a 20-Hz repetition rate of the laser. Ablation occurred only when the tip was held in contact with the tissue. CONCLUSIONS: The technology described herein appears to be advantageous and applicable to a variety of vitreoretinal surgical procedures.

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Pattern-reversal electroretinograms were used as an objective measure of macular integrity in a subset of 42 patients who were randomly assigned at enrollment in the Macular Photocoagulation Study to receive laser photocoagulation or no treatment for a subfoveal neovascular lesion. Pattern-reversal electroretinograms were obtained before randomization, three months and six months after randomization, and at six-month intervals randomization, and at six-month intervals thereafter. Responses were obtained to phase-alternating checkerboards of varying check size. Extrapolation of the best-fit regression line relating log-check size to amplitude was used to determine retinal acuity. At each follow-up period, including three months after laser photocoagulation, treated eyes showed less loss in pattern-reversal electroretinographic acuity than untreated eyes. The decline in pattern-reversal electroretinographic acuity in untreated eyes corresponded to the rapid growth in the area of the subfoveal neovascular lesion. The more gradual decline in treated eyes was consistent with an increase in the area of the treatment scar caused by spreading atrophy.

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In an effort to minimize surgical and visual morbidity of cryotherapy for retinopathy of prematurity (ROP), 18 eyes of 13 patients with 3 to 7 clock hours of stage 3 ROP with "plus" disease were treated by cryotherapy applications limited to the avascular retina adjacent to the areas of stage 3 disease. In 17 of 18 eyes, this limited use of cryotherapy was sufficient to cause regression of ROP without further treatments. After at least 3 months follow-up, ROP outcome showed a normal macular appearance in 16 eyes; two eyes developed macular dragging; no retinal detachments occurred.

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To define further the natural history of visual loss in eyes with age-related macular degeneration (ARMD) complicated by a subfoveal neovascular membrane, pattern-reversal electroretinograms (ERGs) were obtained from patients randomized to no treatment at the Dallas center of the Macular Photocoagulation Study (Texas Retina Associates). Study eyes (n = 20) were tested during the initial visit and at 3-, 6-, and 12-month follow-up visits. Responses were obtained to phase-alternating checkerboards of varying check size. Extrapolation of the best-fit regression line relating the logarithm of the check size to amplitude was used to determine "retinal" acuity (log MAR). The pattern-reversal ERG acuity rating (100 - [50 x log MAR]) was derived for each visit. Pattern-reversal ERG acuity ratings for all patients across visits were correlated significantly with visual acuity ratings derived from the Bailey-Lovie chart (r = 0.61, P less than 0.001) and inversely related to neovascular membrane area (r = -0.55, P less than 0.001). During 1 yr of follow-up, pattern-reversal acuity ratings dropped from 53 to 12, corresponding to an average decrease of approximately 0.2 octaves/month. These results suggest that the pattern-reversal ERG, which samples the resolving power of the central 20 degrees, is a sensitive index of visual loss in age-related macular degeneration.

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Thirteen eyes of 55 consecutive patients treated with brachytherapy for malignant melanoma of the choroid developed postirradiation cataracts. Cataract development was more common in older patients and in patients with larger and more anterior tumors. Eleven eyes had extracapsular cataract extraction and intraocular lens implantation. Initial visual improvement occurred in 91% of eyes, with an average improvement of 5.5 lines. Visual acuity was maintained at 20/60 or better in 55% of the eyes over an average period of follow-up of 24 months (range, 6 to 40 months). These data suggest that, visually, cataract extraction can be helpful in selected patients who develop a cataract after brachytherapy for malignant melanoma of the choroid.

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A hydrolysate of yeast RNA (ENCAD) is used in the Soviet Union for the treatment of hereditary retinal degenerations. We report longitudinal data from three young patients who have made at least two visits to the Soviet Union over a five-year period to receive treatment with ENCAD. Two children were diagnosed with cone-rod degeneration and the third has an isolated (simplex) form of retinitis pigmentosa. Visual function measurements were obtained before and after each visit to Moscow. In the comparison of previsit and postvisit visual acuity, 30 Hz flicker amplitude, and visual fields, ENCAD treatment had no significant short-term effect. Despite treatment with ENCAD, each patient has shown a significant decrease in visual function over the 5-year period. The rate of progression in these patients appears similar to previously published data on the natural history of their retinal degenerative disorders.

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Fifteen eyes believed to be at increased risk for macular hole formation underwent vitrectomy in an attempt to prevent macular hole formation. Full-thickness macular holes have not developed in 10 of 11 eyes with stage 1 macular holes. Four eyes were noted to have small full-thickness foveal defects (stage 2 macular holes) at the time of vitrectomy. Two of the four eyes have not progressed to macular hole formation and have 20/25 visual acuity. All patients have been followed for a minimum of 13 months (median, 18 months). The 12 eyes that have not experienced macular hole formation have had a significant (P less than 0.001) improvement in vision with seven (58%) attaining visual acuity of 20/25 or better. The postoperative foveal electroretinogram (ERG) amplitude was higher than the preoperative amplitude in five of the six eyes tested.

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Focal electroretinograms (ERGs) were obtained from the fovea in 142 eyes with a variety of macular diseases and 50 age-matched eyes with acuity loss in which macular disease was ruled out. Across all eyes, the accuracy rate of discriminating macular disease from other causes of acuity loss was 87%. Among all eyes with macular disease, the sensitivity rate of the focal ERG to the presence of macular disease was 85%. Log focal ERG amplitude was significantly correlated with log Snellen acuity, except in those eyes with macular holes. The sensitivity rate increased to 94% when eyes with 20/40 or greater acuity and eyes with macular holes were excluded.

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In a prospective study of macular hole formation, focal electroretinograms (ERGs) were obtained from both eyes of 35 patients with a unilateral, idiopathic, full-thickness macular hole. Foveal cone ERG amplitude was significantly correlated with hole diameter at the initial visit. Twenty-six patients had normal foveal cone ERGs in the fellow eye at the baseline visit and for the duration of the study (mean follow-up, 35 months; range, 24 to 56 months). None of these eyes developed a macular hole. Seven eyes had significantly reduced foveal cone ERGs in the fellow eye, despite good visual acuity and a normal-appearing macula on the initial visit. Four of these eyes subsequently developed a full-thickness macular hole during follow-up (mean follow-up, 35 months; range, 25 to 46 months). Foveal ERG amplitude was significantly related to subsequent macular hole formation, suggesting that this test can provide an objective measure of macular function to help identify eyes at risk for macular hole formation.

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Focal cone electroretinograms were obtained with a 3-degree flickering stimulus from 100 normal eyes and 134 eyes with known macular disease. Responses were obtained during direct visualization of the fundus with a hand-held stimulator-ophthalmoscope. Mean foveal cone amplitude for 100 normal eyes was 0.31 microV, with 95% of all amplitudes greater than 0.18 microV. There was a significant inverse correlation between amplitude and age for responses obtained from the fovea (r = -0.91; p less than 0.001) but not for responses obtained from the parafovea (midway between fovea and disk, r = -0.53; not significant). In eyes with known maculopathy, mean foveal cone amplitude was correlated with Snellen acuity. Even after correcting for normal decreases in amplitude with age, responses were significantly reduced in 88/94 (94%) of all eyes with 20/40 or poorer acuity, suggesting that the focal electroretinogram is a sensitive test for detecting macular disease.

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