The human gene for apurinic/apyrimidinic endonuclease (HAP1): sequence and localization to chromosome 14 band q12.
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Biomedical subjects
Publications and source records attributed to B C Chauhan.
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The purpose of this study was to determine the intraocular pressure characteristics in glaucoma suspects and patients whose visual fields were classified as stable or progressing over a long-term follow-up. We present data from 64 patients who received either medical or laser treatment and who were followed up for a median of 7.4 years. The visual fields of 27 patients were classified as stable and 37 as progressing using predetermined criteria on either the Tübinger or Goldmann perimeter. Patients with initially normal and initially abnormal fields were analysed separately to avoid bias. There were no significant group differences in the mean, highest or interquartile range of intraocular pressure in the follow-up. The largely overlapping distributions over a wide spectrum of the pressure variables in patients with stable and progressing fields show that intraocular pressure alone cannot separate these two groups of patients. Our study does not suggest that pressure reduction in glaucoma has no beneficial effect, but that there may be other factors which determine the fate of the visual field in glaucoma.
The properties of the staircase procedure as applied in automated perimetry were examined. Two computer simulation models were used to vary different test- and patient-related parameters in clinical perimetry. One model was based on the KRAKEN computer simulation program; the other computer simulation was based on stimulus-response data sets from 11 normal subjects. The results were analyzed in terms of efficiency and accuracy. It was found that: (1) in general, there was an efficiency-accuracy trade-off; (2) increases in response fluctuation produced substantially greater errors in threshold estimates; (3) little or no improvements in accuracy were achieved by increasing the number of reversals; (4) the starting position of the staircase relative to the threshold influenced the efficiency of threshold determinations but not their accuracy; (5) a single-response error reduced the efficiency of staircases; (6) the position of a single-response error in a staircase sequence influenced the accuracy and efficiency of the threshold determination; and (7) more than one response error during a staircase sequence always resulted in a marked reduction in accuracy and/or efficiency. Current perimetric strategies appear to be at or near optimal levels, and therefore, strategies in the future may need to depart from a staircase-style procedure to achieve a significant increase in both accuracy and efficiency. Computer simulation studies can provide an effective means of evaluating perimetric test procedures and defining optimum strategies, which then can be verified clinically by subsequent testing in patient populations.
A total of 75 eyes in 75 patients with different types of glaucoma (21 eyes with low-tension glaucoma, 49 with primary open-angle glaucoma and 5 with pigmentary glaucoma) were examined by automated light-sense, flicker and resolution perimetry. All fields were classified in a masked fashion as being "normal" (N) or as having "diffuse loss" (D), "localized loss" (L) or "diffuse plus localized loss" (DL). The frequency distributions for the various field loss categories were plotted against the highest intraocular pressure ever reported in the patients' records. The frequency distribution for the purely localized defects showed a peak at 20 mmHg and were markedly skewed to low pressure values, whereas those for both diffuse plus localized damage and purely diffuse loss peaked at about 30 mmHg. The data suggest that diffuse field loss may be an indicator of pressure-induced damage.
The authors studied the effect of multiple threshold determinations on local and global (root-mean-square) short-term fluctuation in 30 subjects (10 controls, 10 glaucoma suspects, and 10 glaucoma patients) with a mean age of 56.70 years. Five custom programs were designed on the Octopus perimeter in which the total number of threshold determinations was equal but in which thresholds at 2 principal locations were determined between 2 and 15 times. One randomly selected eye of each subject was first tested with the standard Octopus programs G1 and 31 followed by the custom programs. Local fluctuation initially increased with the number of threshold determinations and then stabilized after five determinations. Global fluctuation was not influenced by the number of determinations and the values obtained by the shorter custom programs were not significantly different from those obtained by the standard programs. Programs that determine thresholds only twice at a given location may underestimate local fluctuation. Furthermore, local fluctuation is de-emphasized by the "watering-down" effect of estimating global fluctuation.
The authors studied the effects of threshold, age, and visual field location on intratest variability in 11 normal subjects between the ages of 15 and 50 years (mean, 35.37 years). The subjects were tested with a conventional manual (Tübinger) perimeter and a high-pass resolution (Ring) perimeter at the following locations: (0 degrees, 30 degrees), (0 degrees, 15 degrees), (0 degrees, -15 degrees), and (0 degrees, -30 degrees). Frequency-of-seeing curves were constructed to obtain accurate estimates of threshold and intratest variability. Although location did not have a significant effect on intratest variability in conventional perimetry, intratest variability increased with threshold (P = 0.031) and age (P = 0.012). The results with resolution perimetry contrasted sharply and showed that neither threshold, age, nor location had a significant effect on intratest variability (P greater than 0.225). Although the thresholds with the two types of perimetry were correlated, intratest variability was not. These results show that resolution perimetry may be able to bypass some of the limitations encountered in obtaining thresholds with conventional perimetry, thereby providing more reliable information.
75 eyes of 75 patients with different types of glaucoma (21 eyes with normal-tension glaucoma, 49 eyes with primary open-angle glaucoma and 5 eyes with pigmentary glaucoma) were examined by automated light-sense, flicker and resolution perimetry. All fields were classified as being "normal" (N) or having "diffuse loss" (D), "localized loss" (L) and "diffuse plus localized loss" (DL) in masked fashion. The frequency distributions for the various field loss categories against the highest intraocular pressure ever reported in the patients' records were plotted. The frequency distributions for the purely localized defects show a peak at 20 mmHg and are markedly skewed to low pressure values, while the diffuse plus localized damage and the purely diffuse loss, however, show a peak at about 30 mmHg. The data support the hypothesis that diffuse field loss may be an indicator of pressure-induced damage.
We present results from 64 glaucoma patients and glaucoma suspects followed up for a median period of 7.4 yr who had a median of seven examinations using Program 31 on the Octopus perimeter. The patients also had manual visual fields recorded on either the Tübinger or Goldmann perimeter during the same period. By examining all manual fields over the follow-up, we classified 37 patients as deteriorating and 27 as nondeteriorating by using predetermined field criteria which we believed to be clinically significant. In a masked fashion, the indices mean defect (MD) and corrected loss variance (CLV), in addition to the three cluster analysis indices SIZ, CLUS, and PCLUS were computed for each patient and regressed on time. When a significant positive index/time slope (P less than 0.05) was defined as indication of deterioration, all indices had remarkably poor sensitivities because their slopes did not reach statistical significance in the great majority of patients. When, regardless of statistical significance, positive slopes were defined as indication of deterioration and negative slopes as nondeterioration, the most sensitive index, PCLUS, still had a sensitivity of less than 65%. The indices were better in detecting the presence or absence of visual field deterioration in fields that were initially normal than in those that were initially abnormal. Since the testing modalities of manual and automated perimetry are different, our study was not designed to compare the sensitivity of one technique over the other. Our study does, however, demonstrate that the indices used currently may not be clinically reliable in the assessment of changes in the visual field.
There have been several reports to suggest that the type of visual field damage in open-angle glaucoma is influenced by intraocular pressure (IOP). This study was undertaken to determine the extent to which patients with normal-tension (NTG) and high-tension glaucoma (HTG) could be differentiated on the basis of some features of their visual fields. The results from 40 pairs of NTG and HTG patients were matched closely for the extent of visual field damage, pupil size, and visual acuity. Using this pooled material, the authors increased the IOP difference between the two groups in either direction, ie, by either progressively lowering the highest recorded IOP allowed for inclusion in the NTG group or by progressively increasing that required for inclusion in the HTG group. They compared the normal areas of the patients' visual fields by using simple visual field indices designed to quantify the undisturbed field. Using receiver operating characteristics (ROC) analysis, they showed that changing the inclusion criterion in the NTG group resulted in no better separation between the groups. However, when the inclusion criterion was changed in the HTG group, the two groups tended to become more separable. In this case, the degree of separation appeared to be related to the difference in the highest recorded IOP between the two groups although the separation was not complete. These findings show that pressure has a greater influence on the type of visual field damage at the higher end of the IOP spectrum encountered in open-angle glaucoma and suggest that there is no common single pathophysiologic mechanism in this disease.
We studied the ocular characteristics of 40 pairs of normal-tension and high-tension glaucoma patients who matched closely for the extent of field damage, pupil size, and visual acuity. To determine if there were differences in visual field damage between patients with normal-tension and high-tension glaucoma, we studied characteristics of the areas of the patients' visual fields that were undisturbed. We computed the number of normal locations, the number of clustered normal locations, and the size of the largest cluster of normal locations. The results showed that for an equivalent extent of damage, the individuals in the normal-tension group had greater areas with normal sensitivity, hence more localized damage. A comparison of the patient data to control data showed that paired differences were larger when the normal-tension member of a pair had a larger value in any of the parameters. The results support the hypothesis that glaucoma patients with lower intraocular pressures have more localized damage and those with higher intraocular pressures have more diffuse damage.
We studied the behavior of intraocular pressure in glaucoma suspects randomly selected to receive either topical timolol or no treatment over the course of a long-term prospective follow-up study. All patients who after six years of follow-up showed no localized field defects or disk changes, or whose pressures were not dangerously increased (24 treated and 22 untreated patients), were included in the present study. Overall, the two groups showed an increase in pressure followed by a gentle leveling off and a decrease toward the end of the follow-up period. The pressure-time curves of the two groups were parallel and vertically separated by 4.94 mm Hg. When pressure-time relationships were determined in individual patients, the categorical group differences were not statistically significant. Our results suggest that most glaucoma suspects did not exhibit a random time-course of intraocular pressure and that the effect of treatment was simply to lower the pressure-time curve of the treated group by a fixed level throughout the six-year follow-up period.
We examined the eyes of a group of patients entered into and still continuing in a glaucoma suspect study. Over time, some remained unchanged while others developed chronic open-angle glaucoma (COAG). By comparing the data obtained by ultrasonic measurement of the axial length (A) and central corneal thickness (CCT), along with measurement of intra-ocular pressure (IOP) from these patients and normal control subjects, we found no differences. However, by combining these factors in a calculation of eye-wall stress we found a significant difference between the glaucoma suspect and the future glaucomatous eye.
Cluster analysis in perimetry is a technique used in the evaluation of localised visual field loss. It has previously been applied to suprathreshold data and, unlike the indices currently available to indicate localised loss, it is influenced by the relative positions of individual defects. This paper describes a cluster analysis for use with data from Program 31 of the Octopus perimeter. To demonstrate the technique, sensitivity values of normal 60-year-old subject were altered to simulate localised loss. Illustrative examples of clinical cases are given, showing differing degrees of localised loss that do not influence the corrected loss variance (CLV) but influence the computed cluster parameters. It is hoped that the value of this form of analysis will be demonstrated in clinical follow-up of glaucoma patients.
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The central visual fields of 2165 normal and 106 glaucoma eyes were measured using a threshold related suprathreshold strategy. The effects of altering the cluster radius in normals and glaucoma eyes sheds light on the nature of defects in these two groups. It is estimated that approximately 13% of normals have clusters; the great majority of these individuals have one cluster of two defects. Most clusters in normals are formed artefactually due to angioscotoma and/or physiological variations in the blind spot position. Clusters due to other factors occur rarely. Clusters are found with equal frequencies in the superior and inferior fields in normal eyes, but with a greater frequency in the superior field in glaucoma eyes. The use of clusters in quantification is both sensitive and specific. Using results from this large sample and looking at other visual field properties, it is possible to devise weighted probability indices to score visual fields.
The purpose of this investigation was to test the reliability of the American Optical Non-Contact Tonometer Mark II (NCT II) using the Goldmann Applanation Tonometer (GAT) as the validating instrument. The sample contained 102 consecutive patients from our University Eye Clinic, of whom one-half had 4 NCT II measurements first, followed by 4 GAT measurements; the other one-half had 4 GAT measurements first, followed by 4 NCT II measurements. No significant change in intraocular pressure (IOP) was noted over the measurement sequence with either instrument. There was no significant difference between paired NCT II and GAT readings when the NCT II was used first; however, a highly significant difference between paired readings was obtained when the GAT was used first, indicating that the GAT measurement produced a delayed reduction in the IOP. This effect did not occur with the NCT II. Although the NCT II is shown to have a good overall reliability when compared to the GAT in both protocols, the agreement between any two tonometers may be influenced greatly by the very process of taking a measurement and by the dynamic nature of the IOP.
The visual field results from 104 eyes with early glaucomatous loss and 1860 normal eyes have been used to derive the relationship between sensitivity, specificity and the number of test locations in a visual field screening test. A logarithmic relationship was found between sensitivity and the number of test locations and a linear relationship between specificity and the number of test locations. The results indicate that large numbers of test locations are not required to reach high levels of sensitivity and that clinically it might be better to screen all patients with a few stimuli quickly than to examine carefully those patients who meet a precondition such as raised intraocular pressure or abnormal disc appearance.
This study was undertaken to observe the effect on the differential light sensitivity in glaucoma suspects produced by a long-term reduction in intraocular pressure (IOP) with timolol maleate. The results are taken from an ongoing 6 year follow-up study of glaucoma suspects randomly selected for treatment and nontreatment. We present fine-grid meridional data, recorded every 4 months by automated perimetry, of all 46 patients (24 treated and 22 untreated) who completed the 6 year follow-up without developing localized visual field defects, acquired optic disc changes and whose IOP was not judged clinically dangerous during the follow-up. Methods of analyzing the profile sensitivity, the profile slope and the sensitivity of specific locations over the follow-up are described. The results show that the long-term fluctuation in differential light sensitivity in the two groups was not significantly different (P = 0.395) and that the sensitivity at most of the locations remained stable. The number of stable locations was not significantly different in the two groups (P = 0.412) and there was also no difference in the number of locations where the sensitivity appeared to decrease (P = 0.193) or increase (P = 0.540). Analysis of covariance showed no group difference in the profile sensitivity or the profile slope and that these variables remained stable in both groups over the 6 year period. Although the treated group maintained a consistently lower IOP than the untreated controls, our results showed that long-term pressure reduction with timolol in glaucoma suspects appeared not to influence the differential light sensitivity in the tested meridian.