The retinal nerve fiber layer, neuroretinal rim area, and visual evoked potentials in MS.

In a prospective study of 57 patients with clinically definite, probable, or possible multiple sclerosis (MS), one-half of whom had a history of optic neuritis, retinal nerve fiber layer (RNFL) defects and the neuroretinal rim (NRR) area were quantitatively determined and compared with the visual evoked potential (VEP). There were abnormal VEP latencies in 63% of all patients (definite and probable = 68%, possible = 50%); local or diffuse RNFL defects in 54%, (definite and probable = 54%, possible = 50%); and an abnormally small NRR area in 30% (definite and probable = 32%, possible = 25%). Abnormalities in one or more of the VEP, RNFL, or NRR area occurred in 86% of all patients (definite and probable = 90%, possible = 75%), thus considerably increasing the yield of optic nerve abnormalities over that of the VEP alone. The predominance and extent of the diffuse RNFL defects, which are axonal abnormalities, suggest a more diffuse optic nerve pathology in MS than can be accounted for by a "plaque" pathology and indicate that extensive axonal loss commonly occurs in the optic nerves of MS.

The influence of intraocular pressure on visual field damage in patients with normal-tension and high-tension glaucoma.

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.

The effect of long-term intraocular pressure reduction on the differential light sensitivity in glaucoma suspects.

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.

The use of visual field indices in detecting changes in the visual field in glaucoma.

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.

Quantification of glaucomatous visual field defects with automated perimetry.

A method to quantify different glaucomatous visual field defects is presented. Three visual field indices are calculated: the short-term fluctuation, the mean defect, and the corrected loss variation. The method was applied to visual fields tested with program JO on the Octopus automated perimeter. The indices of 130 glaucoma suspects and 50 glaucoma patients were compared with 100 normal controls. The indices provide good detectability of visual field defects and easy follow-up.

Estimation of the short-term fluctuation from a single determination of the visual field.

The short-term fluctuation in regular grid threshold static fields is commonly determined from repeated observations of a number of threshold points. In this study we estimated the short-term fluctuation from a single determination of the field. Sixty-two eyes of 62 patients were tested, using three consecutive repetitions of a Humphrey 24-2 full threshold program. The resulting grid patterns were examined using a modified version of the statistical technique of trend-surface analysis. Polynomial surfaces of increasing degree were fitted to the data over the grid. The residual variances after detrending the surface correlated very well with the direct estimates based on the triple observations at each point (correlation coefficients of log-transforms of 0.8 and better). We conclude that short-term fluctuation (the square root of the variance) can be estimated with good reliability from grids of single threshold determinations.

Pattern electroretinograms from hemifields in normal subjects and patients with glaucoma.

PURPOSE: Because glaucomatous visual field loss predominantly occurs in one hemifield, a baseline ratio of pattern electroretinogram (PERG) hemifield amplitudes (upper field:lower field) was determined in normal subjects and then examined in patients with glaucoma. METHODS: In 26 normal subjects and eight patients with glaucoma with typical arcuate field loss involving the test area (central 20 degrees), hemifield PERGs were recorded using checkerboard screens of check size 0.5 degrees and frequency 3.75 reversals per second (transient) and 15 reversals per second (steady state). RESULTS: The ratios obtained for normal central upper:lower amplitudes were 0.95 +/- 0.13 (transient) and 0.93 +/- 0.10 (steady state Fourier second harmonic). Wide nasal-field (52 degrees x 42 degrees) PERG ratios recorded on two subjects confirmed that the ratio held across large retinal areas. The ratio did not change with age or check size. The ratio showed less variability between patients than PERG amplitudes. In the patients with glaucoma, the hemifield PERG amplitude correlated with summed visual field thresholds for that area. Patients with glaucoma could be discriminated from normals by an abnormal ratio (> 2 SD) in seven of the eight patients. In two additional patients with more peripheral scotomas, the ratio remained normal. CONCLUSIONS: In normals, the upper:lower hemifield PERG ratio is slightly < 1.0 and remains stable with age. In glaucoma, visual field defects are associated with PERG reductions in the corresponding hemifield. An abnormal PERG hemifield ratio can be found in many patients, although more peripheral and symmetrical losses may still be missed.

Comparison of psychophysical and electrophysiological testing in early glaucoma.

PURPOSE: To compare the sensitivity and specificity of a wide range of psychophysical and electrophysiological tests in the detection of early glaucomatous damage. METHODS: Forty-three normals and 43 patients with early glaucoma, some still without field defects, were tested with differential light threshold perimetry, short-wavelength automated perimetry, high-pass resolution perimetry, motion detection, flicker contrast sensitivity, flickering and isoluminantly matched letter tests, and pattern and flash electroretinography, including photopic, scotopic, oscillatory potentials, and 30 Hz flicker. Receiver operating characteristic analysis was applied to continuous variables derived from each of the tests. RESULTS: Most parameters reflected glaucomatous loss to some degree, even though only single variables were analyzed separately in the receiver operating characteristic analysis. The pattern electroretinogram and some of the letter acuity tests had the best sensitivity and specificity, followed by short-wavelength automated perimetry and high-pass resolution-perimetry. Motion detection, flicker contrast, and flash electroretinogram parameters scored poorly. Six patients with normal results on the Humphrey field test had abnormal results on many of the other tests. CONCLUSIONS: Applying different psychophysical and electrophysiological tests may add to our ability to detect early glaucomatous damage.

Sensitivity and specificity of a diagnostic test determined by repeated observations in the absence of an external standard.

Traditionally, the sensitivity and specificity of a new diagnostic test are derived from its application to two groups of individuals known to have or not to have met the criterion to be detected as judged by means of a "gold standard", some external time-honored test. In this study, a test with unknown accuracy parameters was used to detect an end-point criterion in an ongoing ophthalmological clinical trial. Since no external test method was available to assess the accuracy of this test, equations were derived relating the unknown sensitivity and specificity of the test to data frequencies based on replicate measurements. The solutions to these equations also provided estimates of the incidence rate of the criterion under investigation in the group tested, and of the predictive values of the test. The validity of this method of estimation is discussed, and applications to other situations are suggested.

The visual field of low tension glaucoma and shock-induced optic neuropathy.

The visual fields of patients with shock-induced optic neuropathy with excavation, low tension glaucoma, and chronic simple glaucoma were analyzed. True altitudinal defects are seldom found. The three disease states showed identical field defects. Subtle defects can occur in all three disease states. The preponderance of defects occurred in the upper field. There are obvious differences from ischemic optic neuropathy.

Correlation between color vision scores and quantitative perimetry in suspected glaucoma.

The mean differential threshold, studied on the Octopus perimeter, and color vision, estimated by the Farnsworth-Munsell 100-Hue test, were studied in glaucoma suspects and patients with questionable early field defects. The results of both tests were significantly correlated. The color vision scores correlated with the central, paracentral, and midperipheral parts of the visual field. This result suggests that both functions are disturbed in glaucoma and that the disturbance may be present diffusely throughout the visual field.

Comparison between pilocarpine and timolol on diurnal pressures in open-angle glaucoma.

In 14 eyes with open-angle glaucoma, 2% pilocarpine hydrochloride given four times a day was compared with timolol given twice daily in its effect on intraocular pressure around the clock. The findings suggest that the timolol produced a greater reduction in pressure than pilocarpine and that, in 50% of the diurnal curves, the timolol curve showed smaller swings in IOP.

Computerized profile perimetry in glaucoma.

The new profile testing mode of the COMPETER automatic perimeter was clinically tested and compared with careful manual profile perimetry on the Tübinger perimeter. Each of 110 patients with glaucomatous field defects, patients with suspected glaucoma, and normal subjects had one meridian tested. All of the 55 patients who showed an abnormal result on the manual profile also had abnormal findings on the automatic test. Two (4%) of the profiles labeled as normal on initial manual perimetry were identified by the automatic perimeter to be abnormal, and these defects were confirmed on repeated manual profile perimetry. The automatic perimetry gave five (9%) false-positive results in the 53 normal manual profiles, thus giving a specificity of 91%. In two of these cases, the automatic profile indicated defects in areas where the manual profile appeared normal, but there was abnormality in the manual kinetic perimetry in the affected area. The automatic profiles of the COMPETER automatic perimeter are accurate, sensitive, time-saving, and clinically useful.

Early visual field disturbances in glaucoma.

Twenty-two eyes of 22 patients with initially normaly visual fields developed glaucomatous field defects. In 13 of these, the development of the definitive field defect was preceded by a localized minor disturbance in the area where the defect appeared subsequently. In a control group of 22 ocular hypertensives without field defects, six eyes had localized disturbances similar to those that preceded the field defects in the study group. This type of minor localized disturbance may represent an early glaucomatous visual change detectable before the appearance of definitive scotomas.

A clinical comparison of three computerized automatic perimeters in the detection of glaucoma defects.

The ability to detect glaucomatous field defects of three automatic computerized perimeters (COMPETER, OCTOPUS, and PERIMETRON) was compared in a clinical study of 74 patients. This study included patients with glaucoma, those with suspected glaucoma in whom the visual fields were completely normal, and normal subjects. The reference fields were obtained by careful static and kinetic manual perimetry on the Tübinger perimeter. All the automatic instruments gave similar high rates of detection of visual field loss and low false-positive test results. Quantity conventional manual perimetry is necessary to support automatic perimetric results, but automatic perimeters already can do a large proportion of routine perimetric screening.

Features of the optic disc in preglaucomatous eyes.

Sixteen preglaucomatous eyes in which glaucomatous field defects developed were compared with 38 preglaucomatous eyes matched for age and sex whose fields remained normal. A noticeable enlargement of the cup occurred in 31% of those in which field loss developed. The cups of those in whom visual field defects developed were larger than in the controls, thus suggesting early acquired tissue damage preceding field loss. Field defects developed without noticeable enlargement and with a small initial cup in 12% of those observed, and these would not have been suspected from the initial disc appearance.

Neuroretinal rim area and retinal nerve fiber layer in glaucoma.

Magnification corrected measurements of the neuroretinal rim area of the optic nerve head were correlated with semiquantitative scores of diffuse and localized loss of retinal nerve fibers. The study comprised 134 patients, including 33 normal control subjects, 50 patients with suspected glaucoma, and 51 patients with glaucoma. Both of these estimates of the amount of neural tissue in the eye were highly significantly correlated with the rim area, with the diffuse nerve fiber loss score having somewhat higher correlation coefficient than the localized nerve fiber loss score.

Effect of acetazolamide on the differential threshold.

Following the oral administration of three 250-mg doses of acetazolamide sodium to nine patients with glaucomatous visual-field defects, a statistically significant improvement in the differential threshold was observed, whereas in 16 glaucoma suspects, no change could be detected. The greatest improvements following acetazolamide administration occurred in younger patients and in those with the greatest disturbances of the visual field.

Covariates of the long-term fluctuation of the differential light threshold.

The scatter of the differential light threshold has a short-term and a long-term component. Although these components are significantly positively correlated, the relationship is not strong enough to accurately predict in an individual patient the long-term fluctuation from the short-term fluctuation. The reversible variation of the retinal sensitivity with time is statistically related to the temporal variation of the short-term scatter, to the variation in reaction time, and probably to the variation in the intraocular pressure.

Differential light threshold. Short- and long-term fluctuation in patients with glaucoma, normal controls, and patients with suspected glaucoma.

In the diagnosis and evaluation of progression of chronic open-angle glaucoma, a quantitative comparison of visual fields is important for which a knowledge of the spontaneous fluctuation of the visual field is essential. This study shows that in patients with glaucoma, the components of the short- and long-term fluctuation are substantially greater than in patients without the disease. Patients with suspected glaucoma show fluctuation in between, and all components of the fluctuation are greater in them than in normals and smaller than in patients with open-angle glaucoma.