Search PubMed⌕ Search

Biomedical subjects

Chris A Johnson

Publications and source records attributed to Chris A Johnson.

At least 37 records · Page 2Linked to original sources

Flavin-dependent antioxidant properties of a new series of meso-N,N'-dialkyl-imidazolium substituted manganese(III) porphyrins.

A number of synthetic manganese complexes exhibit both in vitro and in vivo catalytic antioxidant activities. This study reports that the antioxidant potencies of a new series of meso-N,N'-dialkyl-imidazolium substituted manganese(III) porphyrins are dependent, in part, on their ability to redox cycle with endogenous flavin-dependent oxidoreductases. Inhibition of lipid peroxidation activities of these novel cationic porphyrins was compared using rat brain homogenate as a source of lipids and endogenous oxidoreductases. Iron and ascorbate was used as initiators of lipid peroxidation, and two indices of lipid peroxidation (thiobarbituric acid reactive species (TBARS) and F(2)-isoprostanes) were determined. All meso-N,N'-dialkyl-imidazolium substituted porphyrins tested were potent inhibitors of lipid peroxidation with IC(50) ranging from 0.1 to 34 microM with a metal-dependent potency of Mn(III)>>Co(III)>Zn(II). A flavin-dependent oxidoreductase antioxidant process was supported by the ability of the diphenyleneiodonium chloride (DPI, a flavoenzyme inhibitor) to decrease the potency of Mn-porphyrins in the lipid peroxidation model and that Mn-porphyrins stimulate NADPH oxidation in rat brain homogenates. These data suggest that metalloporphyrins may have differential antioxidant effects in tissues due to the presence or absence of flavin-dependent oxidoreductases.

Animals↗

Clinical trial of docosahexaenoic acid in patients with retinitis pigmentosa receiving vitamin A treatment.

OBJECTIVE: To determine whether a therapeutic dose of docosahexaenoic acid (DHA), an omega-3 fatty acid, will slow the course of retinal degeneration in adult patients with retinitis pigmentosa who are also receiving vitamin A. DESIGN: Randomized, controlled, double-masked trial of 221 patients, aged 18 to 55 years, evaluated over a 4-year interval. Patients were given either 1200 mg/d of docosahexaenoic acid or control capsules. All were given 15 000 IU/d of vitamin A (given as retinyl palmitate). Randomization considered genetic type and baseline dietary omega-3 fatty acid intake. MAIN OUTCOME MEASURES: The primary outcome measure was the total point score for the 30-2 program of the Humphrey field analyzer; secondary outcome measures were the total point score for the 30-2 and 30/60-1 programs combined, 30-Hz electroretinogram amplitude, and Early Treatment Diabetic Rentinopathy Study visual acuity. RESULTS: No significant differences in decline in ocular function were found between the docosahexaenoic acid plus vitamin A (DHA + A) group and control plus vitamin A (control + A) group over a 4-year interval among all 221 randomized patients or among the 208 patients who completed all 4 follow-up visits. The mean annual rate of loss of sensitivity for the Humphrey Field Analyzer 30-2 program was 37 dB for the DHA + A group and 38 dB for the control + A group (P =.88). For the Humphrey Field Analyzer 30-2 and 30/60-1 programs combined, the mean annual rates of loss of field sensitivity were 57 dB for the DHA + A group and 60 dB (P =.73) for control + A group. No toxic adverse effects were observed. No significant differences by treatment group assignment were observed within genetic types or within the category of baseline omega-3 fatty acid intake. CONCLUSION: In patients assigned to receive 15 000 IU/d of vitamin A, this randomized trial showed that 1200 mg/d of docosahexaenoic acid supplementation over a 4-year interval did not, on average, slow the course of disease in patients with retinitis pigmentosa.

Administration, Oral↗

Further evaluation of docosahexaenoic acid in patients with retinitis pigmentosa receiving vitamin A treatment: subgroup analyses.

OBJECTIVE: To determine whether docosahexaenoic acid will slow the course of retinal degeneration in subgroups of patients with retinitis pigmentosa who are receiving vitamin A. DESIGN: A cohort of 208 patients with retinitis pigmentosa, aged 18 to 55 years, were randomly assigned to 1200 mg of docosahexaenoic acid plus 15 000 IU/d of vitamin A given as retinyl palmitate (DHA + A group) or control fatty acid plus 15 000 IU/d of vitamin A (control + A group) and followed up over 4 years. Seventy percent of the patients in each group were taking vitamin A, 15 000 IU/d, prior to entry. We compared rates of decline in ocular function in the DHA + A vs control + A groups among the subgroups defined by use or nonuse of vitamin A prior to entry. We also determined whether decline in ocular function was related to red blood cell phosphatidylethanolamine docosahexaenoic acid level, dietary omega-3 fatty acid intake, or duration of vitamin A use. Main outcome measures were Humphrey Field Analyzer visual field sensitivity, 30-Hz electroretinogram amplitude, and visual acuity. RESULTS: Among patients not taking vitamin A prior to entry, those in the DHA + A group had a slower decline in field sensitivity and electroretinogram amplitude than those in the control + A group over the first 2 years (P =.01 and P =.03, respectively); these differences were not observed in years 3 and 4 of follow-up or among patients taking vitamin A prior to entry. In the entire cohort, red blood cell phosphatidylethanolamine docosahexaenoic acid level was inversely related to rate of decline in total field sensitivity over 4 years (test for trend, P =.05). This was particularly evident over the first 2 years among those not on vitamin A prior to entry (test for trend, P =.003). In the entire control + A group, dietary omega-3 fatty acid intake was inversely related to loss of total field sensitivity over 4 years (intake, <0.20 vs > or =0.20 g/d; P =.02). The duration of vitamin A supplementation prior to entry was inversely related to rate of decline in electroretinogram amplitude (P =.008). CONCLUSIONS: For patients with retinitis pigmentosa beginning vitamin A therapy, addition of docosahexaenoic acid, 1200 mg/d, slowed the course of disease for 2 years. Among patients on vitamin A for at least 2 years, a diet rich in omega-3 fatty acids (> or =0.20 g/d) slowed the decline in visual field sensitivity.

Administration, Oral↗

Normative ranges and specificity of the multifocal VEP.

PURPOSE: To describe a normative database for the multifocal VEP (mfVEP) and to evaluate specificity for a range of cluster criteria. METHODS: One hundred persons (62 females and 38 males) with normal visual fields and ranging in age from 21.6 to 92.4 years participated in this study. Self-reported race in 80 of these 100 persons was 'White or Caucasian,' eight were 'Black or African-American,' eight were 'Asian,' and four were 'Hispanic or Latino.' Pattern-reversal mfVEPs were obtained using a dartboard stimulus pattern in VERIS and two 8-min runs per eye were averaged. A bootstrap technique was used to estimate the normal range of mfVEP response signal-to-noise ratio (SNR) and inter-ocular amplitude ratio at each location. Specificity (1 - false alarm rate) was evaluated for a range of cluster criteria, whereby the number and probability level of the points defining a cluster were varied. RESULTS: There was no overall effect of age on SNR (r2 = 0.16, p = 0.22) nor was the interaction between age and location significant (F = 0.83, p = 0.82, ANOVA). The location with the largest age effect had an r2 of only 0.13. There was a small but significant effect of sex (t = 2.1, p = 0.04) such that SNR was slightly (11%) larger in females than males, but there was no significant interaction between sex and age (t = 0.82, p = 0.41). There was a slight trend toward higher SNR in the Asian group and lower SNR in the African-American group, but the overall effect of race was not significant (F = 1.99, p = 0.12). Specificity depended on the number and probability level of the points defining a cluster. Specificity did not vary by age group in a simple monotonic manner. False positive rates were slightly higher in females than males, and slightly higher in the African-American group as compared with the Asian group. CONCLUSIONS: Excellent specificity can be achieved for the mfVEP by using particular cluster criteria for monocular and inter-ocular tests. The effects of age, sex, and race were all very small and only the effect of sex was statistically significant. This normative database can be used for analyses of mfVEP results from individual patients with little risk that demographic factors such as age and sex will confound diagnostic accuracy.

Adult↗

Determining abnormal interocular latencies of multifocal visual evoked potentials.

PURPOSE: To describe methods for measuring interocular latency differences of multifocal visual evoked potentials (mfVEP) and for determining regions with abnormal interocular latencies in patients. METHODS: The mfVEPs from 100 individuals with normal visual fields and normal fundus examinations were analyzed. Individuals ranged in age from 21.6 to 92.4 years. The stimulus was a 60 sector, pattern-reversing dartboard display. Each sector had 16 checks, 8 white (200 cd/m2) and 8 black (< 1 cd/m2). Interocular latency was measured as the temporal shift producing the best cross-correlation value between the corresponding responses of each eye. The 'corrected interocular latency' was defined as the difference between this shift and the mean interocular latency (shift) for a particular sector and recording channel. RESULTS: The variability of the corrected interocular latency decreased as the signal-to-noise ratio (SNR) of the mfVEP responses increased. For example, the 95% confidence intervals decreased from over 16 ms to under 4 ms as SNR increased. Grouping and summing the responses also lead to an increase in SNR and a decrease in the confidence interval. The results of various cluster criteria were also derived. A cluster criterion (e.g. two or more contiguous points within a hemisphere exceeding a given confidence interval), can serve to increase the specificity for detection of eyes or individuals with abnormal interocular latencies. For example, while 21% of the eyes had 3 or more points exceeding the 5% confidence interval, only 1.8% of the eyes had a cluster of 3 or more of these points. Finally, interocular latency was only weakly correlated with age (r = 0.26). CONCLUSION: In testing for abnormalities in interocular latencies, the confidence interval should be based upon the SNR of the response. Grouping and summing responses to increase SNR or employing a cluster test may also prove useful.

Acute Disease↗

Determining abnormal latencies of multifocal visual evoked potentials: a monocular analysis.

PURPOSE: To describe a methodology for measuring abnormal timing of monocular multifocal visual evoked potentials (mfVEP). METHODS: The mfVEPs from 100 individuals with normal visual fields and normal fundus exams were analyzed. The stimulus was a 60 sector, pattern-reversing dartboard display. For each of the 60 locations of the dartboard and each channel and each eye, a template was derived based upon the average of the responses from the 100 normal individuals. In deriving this template, care was taken to exclude those responses reversed in polarity as compared to the average response. The best array of responses for each individual was compared to these templates. The relative latency of each response was measured as the temporal shift producing the best cross-correlation value. RESULTS: The 95% confidence interval (CI) decreased as the signal-to-noise ratio (SNR) of the mfVEP responses increased. For example, the 95% CI decreased from over 17 ms to under 9 ms as the SNR increased. Grouping and summing the responses also lead to an increase in SNR and a decrease in CI. Because the number of points exceeding the CI is not randomly distributed among normal individuals, a cluster criterion (e.g. two or more contiguous points within a hemisphere exceeding a given confidence interval) can be helpful. For example, while 18% of the eyes had 5 or more points exceeding the 5% confidence interval, only 6.5% of the eyes had a cluster of 5 of these points. The correlation between relative latency and age was relatively low (r = 0.46). CONCLUSION: For detecting abnormalities in the timing of monocular, mfVEP responses, a template method provides a reasonable approach. In devising a particular test for abnormal timing, the CI should be based upon the SNR of the response. In addition, grouping and summing responses to increase SNR or employing a cluster test may also prove useful.

Acute Disease↗

Classification of visual field abnormalities in the ocular hypertension treatment study.

OBJECTIVES: (1) To develop a classification system for visual field (VF) abnormalities, (2) to determine interreader and test-retest agreement, and (3) to determine the frequency of various VF defects in the Ocular Hypertension Treatment Study. METHODS: Follow-up VFs are performed every 6 months and are monitored for abnormality, indicated by a glaucoma hemifield test result or a corrected pattern SD outside the normal limits. As of January 1, 2002, 1636 patients had 2509 abnormal VFs. Three readers independently classified each hemifield using a classification system developed at the VF reading center. A subset (50%) of the abnormal VFs was reread to evaluate test-retest reader agreement. A mean deviation was calculated separately for the hemifields as an index to the severity of VF loss. MAIN OUTCOME MEASURES: A 97% interreader hemifield agreement. RESULTS: The average hemifield classification agreement (between any 2 of 3 readers) for 5018 hemifields was 97% and 88% for the 1266 abnormal VFs that were reread (agreement between the first and second classifications). Glaucomatous patterns of loss (partial arcuate, paracentral, and nasal step defects) composed the majority of VF defects. CONCLUSION: The Ocular Hypertension Treatment Study classification system has high reproducibility and provides a possible nomenclature for characterizing VF defects.

Antihypertensive Agents↗

A computerized method of visual acuity testing: adaptation of the early treatment of diabetic retinopathy study testing protocol.

PURPOSE: To develop a computerized method of visual acuity testing for clinical research as an alternative to the standard Early Treatment for Diabetic Retinopathy Study (ETDRS) testing protocol, and to evaluate its test-retest reliability and concordance with standard ETDRS testing. DESIGN: Test-retest reliability study. METHODS: Multicenter setting of a study population of 265 patients at three clinical sites. Visual acuity was measured with both the electronic visual acuity testing algorithm (E-ETDRS) and standard ETDRS protocol (S-ETDRS) twice on one eye of each patient. E-ETDRS testing was conducted using the electronic visual acuity tester (EVA), which utilizes a programmed Palm (Palm, Inc, Santa Clara, California, USA) hand-held device communicating with a personal computer and 17-inch monitor at a test distance of 3 meters. RESULTS: For the E-ETDRS protocol, test-retest reliability was high (r = 0.99; with 89% and 98% of retests within 0.1 logMAR and 0.2 logMAR of initial tests, respectively) and comparable with that of S-ETDRS testing (r = 0.99; with 87% and 98% of retests within 0.1 logMAR and 0.2 logMAR of initial test, respectively). The E-ETDRS and S-ETDRS scores were highly correlated (r = 0.96 for initial tests and r = 0.97 for repeat tests). Based on estimates of 95% confidence intervals, a change in visual acuity of 0.2 logMAR (10 letters) from a baseline level is unlikely to be related to measurement variability using either the E-ETDRS or the S-ETDRS visual acuity testing protocol. CONCLUSIONS: The E-ETDRS protocol has high test-retest reliability and good concordance with S-ETDRS testing. The computerized method has advantages over the S-ETDRS testing in electronically capturing the data for each tested letter, requiring only a single distance for testing from 20/12 to 20/800, potentially reducing testing time, and potentially decreasing technician-related bias.

Adolescent↗

Structure and function evaluation (SAFE): II. Comparison of optic disk and visual field characteristics.

PURPOSE: To evaluate the relationship between glaucomatous structural damage to the optic nerve and development of visual field loss with standard automated perimetry (SAP) and short wavelength automated perimetry (SWAP). DESIGN: Cohort study. METHODS: Patients with elevated intraocular pressure and normal SAP visual fields were enrolled in this prospective study. Stereo optic disk photographs, SAP, and SWAP visual fields were obtained annually over a period of 4 or more years. Trained readers evaluated baseline and follow-up optic disk photographs for evidence of glaucomatous damage. Standard automated perimetry and SWAP examinations were evaluated according to previously validated criteria for development of confirmed visual field changes. RESULTS: Two-hundred ninety-five subjects (479 eyes) were enrolled. Following masked assessment of stereo photographs by an optic disk reading center, 272 of the 479 eyes were judged to have glaucomatous optic neuropathy at the time of study entry. Depending on the criteria employed, approximately 10% to 17.5% of all eyes developed confirmed visual field loss for SAP (conversions). Of the conversions, 75% to 80% had baseline glaucomatous optic disk damage, whereas normal and glaucomatous optic disks were equally divided (50%) among the nonconversion eyes. This difference was statistically significant (P <.003). Depending on the criteria employed, 4% to 12% of the eyes had confirmed SWAP deficits at baseline, and 4% to 8% developed confirmed SWAP defects at a follow-up examination. There was a greater percentage of eyes with a glaucomatous optic neuropathy in the group with SWAP deficits (75%-100%) than for those eyes in which SWAP remained normal (45%-60%). Some of these differences were statistically significant (P <.05). CONCLUSIONS: A strong relationship exists between glaucomatous optic disk damage at study entry and the subsequent development of a confirmed glaucomatous SAP visual field defect. A higher percentage of glaucomatous optic disks were also found in patients with SWAP deficits at baseline and in those who later developed SWAP deficits. These findings support the premise that a glaucomatous optic disk is predictive of the subsequent development of glaucomatous visual field loss.

Follow-Up Studies↗

Frequency-doubling technology perimetry.

The FDT perimeter is a compact and relatively inexpensive perimeter whose transportability, tolerance to refractive errors, and rapid test times (less than 1 minute per eye) make it a suitable candidate for visual field screening. It is a uniform finding that the C-20-1 screening protocol of the FDT perimeter provides good sensitivity and specificity for the detection of moderate and severe losses in glaucoma. Sensitivity can be increased by use of the C-20-5 screening protocol. In addition, the FDT perimeter demonstrates good sensitivity and specificity for detecting the presence of neuro-ophthalmic disorders, though it may have a limited ability to determine whether a field defect is hemianopic. There is only limited evidence that the FDT can appropriately detect retinal disease. Despite some evidence that the current FDT perimeter may be suitable for staging and monitoring the progression of visual field damage, the large targets used in the test make this of limited practicability. The development of a frequency-doubling test with smaller targets spaced over narrower intervals would improve the ability of FDT perimetry to determine the spatial extent of visual field defects.

Glaucoma↗

Appearance of the frequency doubling stimulus in normal subjects and patients with glaucoma.

PURPOSE: To determine whether the spatial structure of the frequency doubling technology (FDT) perimetry stimulus is visible at detection-contrast threshold in normal observers and those with glaucoma and to assess its perceived spatial frequency at threshold and suprathreshold contrast. METHODS: Three subject groups were assessed: 10 young normal observers (aged <40 years), 10 older normal observers (aged >50 years), and 10 subjects with glaucoma. Detection thresholds for centrally and eccentrically presented 10 degrees squares, 0.25-cyc/deg, 25-Hz counterphase flicker sine-wave gratings were obtained by using a yes-no staircase procedure. Eccentric locations were in areas of loss of FDT sensitivity (< or =21 degrees ) in subjects with glaucoma, or at 7 degrees or 21 degrees inferonasally in normal observers. Resolution-contrast thresholds were determined by a two-alternative, forced-choice staircase procedure in which subjects selected the orientation of the grating stimulus tilted at +/-45 degrees. Perceived spatial frequency was determined by having subjects alter the spatial frequency of a temporally interleaved stationary sine-wave grating to match the FDT stimulus. RESULTS: No significant difference was found between detection- and resolution-contrast thresholds, implying that spatial structure was visible at detection threshold. In general, subjects perceived the spatial structure to have a spatial frequency closer to doubled than to veridical, although the young normal subjects reported a lower apparent spatial frequency than older individuals. CONCLUSIONS: When instructed as for clinical testing, subjects respond to the presence of the structure of the grating, and perceive the FDT stimulus to have a spatial frequency greater than its true spatial frequency. These findings were consistent across both normal observers and those with glaucoma, at both central and eccentric test locations.

Adult↗

Frequency-doubling technology perimetry and optical defocus.

PURPOSE: The frequency-doubling technology (FDT) perimeter has no provision for introducing corrective lenses, save for the patient's spectacles, and so patients are sometimes tested in the presence of moderate levels of defocus. The effect of defocus on frequency-doubling (FD) sensitivity was determined for both the commercially available instrument and for smaller targets that may be useful in spatially localizing visual field defects. In addition, whether stimulus artifacts may be detectable in the presence of defocus was assessed. METHODS: Detection and resolution thresholds for FD stimuli, along with detection thresholds for spatially uniform flickering stimuli, were measured in normal observers in the presence of up to +6 D of defocus. In addition, the effect of defocus on the summary indices (mean deviation [MD], and pattern standard deviation [PSD]) of both the commercial FDT perimeter and a customized perimeter with smaller, higher spatial frequency targets was determined. RESULTS: Thresholds for conventional FD targets (0.25 cyc/deg, 25 Hz) increased 0.1 log unit with +6 D defocus, whereas thresholds for smaller, higher spatial frequency (0.5 cyc/deg) targets increased 0.4 log unit. Despite the presence of a luminance artifact in the FD stimuli, detection, and resolution thresholds remained coincident at maximum defocus, suggesting that the artifact was not detectable. MD was significantly affected by defocus for the customized FD perimeter only, and PSD was not altered for either the conventional or customized test. CONCLUSIONS: In normal observers, optical defocus has little effect on FDT perimetry sensitivity and does not make low spatial frequency artifacts detectable. Improving the spatial resolution of FDT perimetry decreases its robustness to defocus.

Adult↗

Comparison of different methods for detecting glaucomatous visual field progression.

PURPOSE: To compare the performance characteristics of seven methods for analyzing glaucomatous visual field progression, using a combination of real patient data and computer simulation techniques. METHODS: The initial and final visual field results, separated by 7 years and measured with the full-threshold 30-2 program of the Humphrey Field Analyzer (Carl Zeiss Meditec, Dublin, CA) of 76 patients with open-angle glaucoma were used. A computer simulation program generated 14 interim semiannual visual fields under conditions of high, moderate, and no variability. Progression was analyzed using the methods of the Advanced Glaucoma Intervention Study (AGIS), the Collaborative Initial Glaucoma Treatment Study (CIGTS), three criteria based on the Glaucoma Change Probability (GCP) analysis, and two criteria based on point-wise linear regression analysis (PLRA). Specificities were calculated by using the same visual field of each patient as both the initial and final field (no progression) under conditions of moderate and high variability. RESULTS: Under the no-variability condition, progression rates were 18% for the AGIS, 36% for CIGTS, 47% to 62% for the three GCP methods, and 72% and 84% for the two PLRA methods. Progression rates increased with greater variability with the three GCP methods and decreased with all other methods. The time to detect confirmed progression was longest for the PLRA methods and shortest for the CIGTS and GCP methods. Under the moderate-variability condition, all methods yielded high specificity. The AGIS, CIGTS, and one of the GCP and PLRA methods were relatively resistant to high variability and maintained high specificities. CONCLUSIONS: The AGIS and CIGTS methods had high specificity, but classified fewer cases of progression than the other methods. The GCP methods determined progression earliest; however, they were generally not as specific. Methods based on PLRA were specific but times to confirmed progression were the longest.

Computer Simulation↗

Properties of perimetric threshold estimates from full threshold, ZEST, and SITA-like strategies, as determined by computer simulation.

PURPOSE: To investigate the accuracy and precision of threshold estimates returned by two Bayesian perimetric strategies, staircase-QUEST or SQ (a Swedish interactive threshold algorithm [SITA]-like strategy) and ZEST (zippy estimation by sequential testing), and to compare these measures with those of the full-threshold (FT) algorithm. METHODS: A computerized visual field simulation model was developed to compare the performance (accuracy, precision, and number of presentations) of the three algorithms. SQ implemented aspects of the SITA algorithm that are in the public domain. The simulation was tested by using standard automated perimetry (SAP) visual field data from 265 normal subjects and 163 observers with glaucomatous visual field loss and by exploring the effect of response variability and response errors on algorithm performance. RESULTS: SQ was faster than FT or ZEST, with a comparable mean error when simulating field tests on patients. Point-wise analysis revealed similar error and standard deviation of error as a function of threshold for FT and SQ. If the initial estimate of threshold for either procedure was incorrect, the means and standard deviations of the error increased markedly. ZEST produced more accurate thresholds than did the other two strategies when the initial estimate was removed from the true threshold. CONCLUSIONS: When simulated patients made errors, the accuracy and precision of sensitivity estimates were poor when the initial estimate of threshold either overestimated or underestimated the true threshold. This was particularly so for FT and SQ. ZEST demonstrated more consistent error properties than the other two measures.

Algorithms↗

Anatomy of a supergroup: does a criterion of normal perimetric performance generate a supernormal population?

PURPOSE: To interpret individual results from automated perimeters, a normative database must be developed. Typically, a set of criteria determines those subjects that may be included in the database. This study examined whether a criterion of normal performance on an established perimeter generates a subgroup with supernormal perimetric performance. METHODS: The right-eye perimetric results of 100 subjects were analyzed. Subjects had visual acuities of 6/12 or better, no history of eye disease, and normal slit lamp biomicroscopic and ophthalmoscopic examinations. Subjects performed test-retest visual field examinations on a Humphrey Field Analyzer (HFA) 24-2 test (Zeiss Humphrey Systems, Dublin, CA), and on a custom frequency-doubling (FD) perimeter with targets spaced in the same 24-2 pattern. RESULTS: Test-retest correlation (Spearman rank correlation coefficients, rs) for mean defect (MD) and pattern SD (PSD) were 0.65 and 0.40 (HFA), and 0.82 and 0.39 (FD perimeter). Three subjects with HFA MDs in the lower 5% had similarly low MDs on retest, whereas no subject was common between the test and retest for the lower 5% of HFA PSD. Correlation between the HFA and FD test results were 0.41 (MD) and 0.05 (PSD). Based on these correlations, the bias introduced into perimetric probability limits were determined, by using Monte Carlo simulations. CONCLUSIONS: Although a criterion of a normal MD may produce a subpopulation with supernormal perimetric performance, a criterion of a normal PSD is less likely to do so. Also, a criterion on one test type is less likely to create a supernormal group on a different test type. The bias introduced into perimetric probability limits is small.

Adult↗

Short-wavelength sensitivity deficits in patients with migraine.

OBJECTIVE: To examine short-wavelength sensitivity in patients with migraine using short-wavelength automated perimetry (SWAP) and Stiles 2-color increment threshold procedures. METHODS: Twenty-five subjects with migraine with (n = 11) and without (n = 14) aura and 20 age-matched headache-free subjects underwent testing. All subjects underwent standard automated perimetry (SAP) and SWAP (using a Humphrey field analyzer; 24-2 presentation pattern). In 2 migraine patients (one with and another without aura), the 2-color increment threshold procedure was used to determine whether sensitivity losses were specific to short-wavelength sensitivity pathways or a generalized loss to multiple pathways. RESULTS: No statistically significant differences between migraine patients and controls were found for mean deviation (MD) or pattern-standard deviation (PSD) for SAP. However, for SWAP, MD and PSD were worse for the migraine group (P =.04). Twelve migraine patients had more than 4 locations with sensitivity worse than the 5% probability level (reference value). Increment threshold determinations in the 2 selected migraine patients indicated a selectively greater loss for short-wavelength sensitivity mechanisms. CONCLUSIONS: Approximately 50% of subjects with migraine (with or without aura) demonstrate SWAP sensitivity losses, at times between migraine events. These findings, in conjunction with previous results for SAP and flicker perimetry, suggest that migraine patients should be excluded from normative databases of visual function, and warrant further investigations of the relationship between migraine and glaucoma.

Adolescent↗

Spatial and temporal processing of threshold data for detection of progressive glaucomatous visual field loss.

OBJECTIVE: To evaluate the effect of spatial and temporal filtering of threshold visual field data on the ability of pointwise linear regression (PLR) to detect progressive glaucomatous visual field loss. METHODS: Longitudinal visual field data (Full-Threshold Program 30-2 test point pattern) were simulated using a computer model of glaucomatous visual field progression. This approach permitted construction of a "gold standard" because matching visual field data without variability could be generated and analyzed. Four clustered progressive defects were produced, consisting of 2, 3, 9, and 18 locations, respectively, each with progression rates of -1 and -2.5 dB/y. Pointwise linear regression was used to identify progressive test locations (criterion for progression of statistically significant slope of < or =-1 dB/y, P<.05). Each visual field series was analyzed after the following 3 procedures: (1) no filtering (unprocessed data), (2) Gaussian spatial possessing (3 x 3 grid), and (3) temporal processing (2 field moving average). The effect of spatial and temporal processing on PLR discriminatory power for progression detection was quantified by comparison with the gold standard. RESULTS: Spatial processing reduced PLR sensitivity to levels below that achieved for analysis of unprocessed data for small progressive defects (< or =9 locations) or at the low true progression rate (-1 dB/y). Under these conditions, spatial processing caused small PLR specificity improvement. Spatial processing only improved PLR sensitivity above unprocessed levels when progressive defects were large and changing rapidly (progression rate of -2.5 dB/y). Temporal processing gave consistent PLR improvement in sensitivity for all defect sizes and true progression rates. Pointwise linear regression sensitivity gain provided by temporal processing allowed progression to be detected 2 to 3 visual fields earlier than for analysis of raw data. Specificity dropped slightly as a result of temporal processing but remained at 89% or above for all conditions studied. CONCLUSIONS: Gaussian spatial processing reduces PLR discriminatory power with low true progression rates or small progressive defect sizes and, therefore, is of limited use for detection of progressive visual field loss. Temporal processing improves the sensitivity of PLR and reduces the number of tests required to detect progressive loss with minimal loss of specificity. CLINICAL RELEVANCE: Image processing techniques can be applied to threshold visual field data to enhance sensitivity or specificity of PLR for the determination of progressive change. This investigation demonstrates that temporal processing may assist with the detection of significant progressive visual field loss with fewer test results than unprocessed data.

Computer Simulation↗

The Ocular Hypertension Treatment Study: a randomized trial determines that topical ocular hypotensive medication delays or prevents the onset of primary open-angle glaucoma.

BACKGROUND: Primary open-angle glaucoma (POAG) is one of the leading causes of blindness in the United States and worldwide. Three to 6 million people in the United States are at increased risk for developing POAG because of elevated intraocular pressure (IOP), or ocular hypertension. There is no consensus on the efficacy of medical treatment in delaying or preventing the onset of POAG in individuals with elevated IOP. Therefore, we designed a randomized clinical trial, the Ocular Hypertension Treatment Study. OBJECTIVE: To determine the safety and efficacy of topical ocular hypotensive medication in delaying or preventing the onset of POAG. METHODS: A total of 1636 participants with no evidence of glaucomatous damage, aged 40 to 80 years, and with an IOP between 24 mm Hg and 32 mm Hg in one eye and between 21 mm Hg and 32 mm Hg in the other eye were randomized to either observation or treatment with commercially available topical ocular hypotensive medication. The goal in the medication group was to reduce the IOP by 20% or more and to reach an IOP of 24 mm Hg or less. MAIN OUTCOME MEASURES: The primary outcome was the development of reproducible visual field abnormality or reproducible optic disc deterioration attributed to POAG. Abnormalities were determined by masked certified readers at the reading centers, and attribution to POAG was decided by the masked Endpoint Committee. RESULTS: During the course of the study, the mean +/- SD reduction in IOP in the medication group was 22.5% +/- 9.9%. The IOP declined by 4.0% +/- 11.6% in the observation group. At 60 months, the cumulative probability of developing POAG was 4.4% in the medication group and 9.5% in the observation group (hazard ratio, 0.40; 95% confidence interval, 0.27-0.59; P<.0001). There was little evidence of increased systemic or ocular risk associated with ocular hypotensive medication. CONCLUSIONS: Topical ocular hypotensive medication was effective in delaying or preventing the onset of POAG in individuals with elevated IOP. Although this does not imply that all patients with borderline or elevated IOP should receive medication, clinicians should consider initiating treatment for individuals with ocular hypertension who are at moderate or high risk for developing POAG.

Administration, Topical↗