Deborah J. Derlacki

Rate of Visual Field Loss in Retinitis Pigmentosa

PURPOSE The authors quantitate the rate of visual field loss in patients with retinitis pigmentosa as it relates to different clinical field phenotypes. PATIENTS AND METHODS Goldmann visual fields were obtained with target V4e in 77 patients and with target II4e in 71 patients who had either isolated or various genetic types of retinitis pigmentosa and who met certain entrance criteria. The visual fields were categorized into five distinct clinical field phenotypes on the basis of their pattern of field loss. Mixed-model methods for the analysis of longitudinal data were used to model the natural logarithm of the visual field area as a function of patient age and clinical field phenotype. The average half-life (time over which half of the remaining field area would be lost) of the visual field area for each phenotype was computed from the results of this analysis. Visual field data were not analyzed for patients with a normal clinical field phenotype (type 1). RESULTS Independent of the field phenotype, average half-life values were 7.3 years for target V4e and 6.8 years for target II4e, which were not statistically different (P = 0.16). Visual fields with partial or complete midperipheral ring scotomas (type 2) and those with only a residual central field (type 4) had a half-life of 9.5 and 9.4 years, respectively, for target V4e, and 8.9 and 8.0 years, respectively, for target II4e. Patients with partial peripheral restriction (type 5) lost visual fields with a half-life of 9.5 years for target V4e and 7.3 years for target II4e. None of these differences in the half-lives between the different phenotypes were statistically significant for either targets V4e or II4e. Fields with a residual central area and remaining temporal and/or nasal islands (type 3) had a half-life of 4.8 years for target V4e and 6.0 years for target II4e. The differences in half-lives between type 3 and each of the other field phenotypes were statistically significant for the V4e target, but not for the II4e target. CONCLUSIONS The results of this study can be useful for counseling patients with retinitis pigmentosa and various visual field phenotypes as to their potential rate of visual field loss.

Spatial-frequency characteristics of letter identification

To investigate the spatial-frequency components that govern letter identification we compared contrast thresholds for three types of visual stimulus (1) standard Sloan letters, (2) Sloan letters that were spatially bandpass filtered by cosine log filters, and (3) D6 patterns (sixth spatial derivatives of Gaussians). Stimuli were presented on a gray-scale display screen of a Macintosh computer-based testing system at temporal frequencies primarily of 2 and 16 Hz. Contrast thresholds were measured in two subjects with normal visual acuity with use of forced-choice staircases. Contrast sensitivity functions for standard Sloan letters and D6 patterns were comparable at a temporal frequency of 16 Hz but differed systematically at a temporal frequency of 2 Hz. The measurement of contrast sensitivity for cosine log filtered letters presented at a temporal frequency of 2 Hz indicated that the object spatial frequency of maximum sensitivity shifted to lower frequencies as letter size decreased, whereas the retinal spatial frequency of maximum sensitivity remained relatively constant. When letters were spatially bandpass filtered at a peak object spatial frequency of 2.5 cycles/letter, then contrast sensitivity functions for letter identification were equivalent to those for D6 patterns at both temporal frequencies. These results suggest that spatially filtered letters may provide a more appropriate test of visual function than do standard letter optotypes.

Properties of the human cone system electroretinogram during light adaptation

Changes in the response characteristics of the flash electroretinogram (ERG) of the human cone system were studied during the time course of adaptation to a cone-isolating ganzfeld background. During light adaptation, the amplitudes of the b- and i-waves increased, while the implicit time of the b-wave decreased. The amplitude of the a-wave and the implicit times of the a- and i-waves did not change systematically during light adaptation. Luminance-response functions for b-wave amplitude were obtained at discrete times following background onset and were analyzed using the hyperbolic equation R/R(max) = L(n)/(L(n) + K(n)). The increase in b-wave amplitude was characterized by increases in R(max), K, and n. The decrease in b-wave implicit time was of a similar magnitude at all flash luminances. The amplitude increase of the i-wave only occurred at moderate flash luminances. The results provide a basis for optimizing the clinical recording of cone-isolated single-flash ERGs.

Rod and Cone Dysfunction in Carriers of X-linked Retinitis Pigmentosa

Carriers of X-linked retinitis pigmentosa were studied using electroretinographic and psychophysical procedures. Under both dark- and light-adapted (cone-isolated) conditions, electroretinogram (ERG) a-waves of carriers were reduced in amplitude but normal in implicit time, whereas b-waves were reduced in amplitude and delayed in implicit time. Reductions in b-wave amplitudes of the carriers as a group were equivalent for the rod and cone systems. Luminance-response functions for both dark-adapted and cone-isolated b-waves were fit by the Naka-Rushton equation and demonstrated a selective reduction of Rmax; the semi-saturation constant (K) and the slope parameter (n) were normal. Electroretinograms recorded using the brightest stimulus flashes were most effective at distinguishing carriers from normals. Absolute thresholds of the carriers were elevated significantly across the central 40 degrees of the visual field. As a group, the threshold elevations of the carriers were approximately equal for the rod and cone systems.

Visual Acuity and Contrast Sensitivity for Individual Sloan Letters

Sloan letter optotypes are used frequently to evaluate visual impairment, and scoring procedures have been developed that are based on the numbers of letters that are identified correctly. However, previous studies have presented conflicting evidence regarding the relative identifiability of the individual Sloan letters. To investigate this issue further, we measured psychometric functions for the identification of each of the 10 Sloan letters, with individual letters presented in random order on the gray-scale display of a Macintosh computer-based testing system. Data were obtained from three visually normal subjects under each of three conditions: (1) as a function of log contrast at a relatively large letter size; (2) as a function of log contrast at a letter size near the acuity limit; and (3) as a function of log MAR (minimum angle of resolution) at maximum letter contrast. Estimates of threshold log contrast and threshold log MAR were derived from best-fitting Weibull functions. Threshold log contrast for small letters showed the greatest interletter variability. There was relatively little interletter variability in either threshold log contrast for large letters or threshold log MAR for high-contrast letters. However, due to the relatively steep psychometric functions under these latter two conditions, the different Sloan letters had considerably different percent correct values near threshold. The overall pattern of results suggests that the contrast sensitivity functions for individual Sloan letters are displaced laterally along a log MAR axis, while their vertical positions are essentially equivalent.

Difficulty in performing everyday activities in patients with juvenile macular dystrophies: comparison with patients with retinitis pigmentosa.

AIMS To ascertain the level of perceived difficulty experienced by patients with central vision loss due to juvenile macular dystrophies in the performance of everyday activities. A second objective was to compare their perceived difficulty with that of patients with retinitis pigmentosa (RP) with primarily peripheral vision loss. METHODS 72 patients with Stargardt disease, cone dystrophy, or cone-rod dystrophy who had visual acuities worse than 20/40 and normal peripheral visual fields rated themselves on their difficulty in the performance of 33 activities encompassing a wide variety of everyday tasks. These findings were compared with the responses of 120 patients with typical RP or Usher syndrome type 2 who had visual acuities of 20/40 or better and peripheral visual field loss. RESULTS The juvenile macular dystrophy group reported the greatest level of overall self perceived difficulty with activities involving central vision, and lesser and variable degrees of difficulty with items within the mobility, negotiating steps, driving, and miscellaneous categories. Consistent with these findings, there were highly significant correlations between subjects’ rated performances of activities involving central vision and the clinical measures of vision, including visual acuity and size of central scotoma. There were fewer significant correlations between perceived performance of activities in the other categories and the clinical measures. In general, those activities that showed significant correlations with the clinical measures of vision for the patients with juvenile macular dystrophies also showed significant differences in the patterns of responses between the juvenile macular dystrophy group and the RP group. Those items which were not correlated with the clinical measures in the juvenile macular dystrophy group tended not to show significant differences in the response patterns between the two groups. CONCLUSION These results provide insight into the types of perceived difficulties in performing tasks of everyday life in patients with these disorders which affect counselling of these patients.

Visual Acuity Impairment in Patients with Retinitis Pigmentosa

PURPOSE The authors evaluated visual acuity impairment in 906 patients from 742 families with either isolated or various identifiable genetic subtypes of retinitis pigmentosa (RP) to determine the severity of their visual acuity impairment. Emphasis was placed on the prevalence of total blindness and visual acuity of 20/200 or worse in this group of patients. METHODS This cross-sectional retrospective study included all patients with RP who met certain entrance criteria and were examined by one of the authors (GAF). The authors analyzed the eye of each patient with the best-corrected visual acuity on their most recent visit. RESULTS Seventeen patients with a sector form of RP were excluded from the authors primary analysis. In the remaining group of 889 patients, 710 (80%) had a visual acuity of better than 20/200, 648 (73%) showed a visual acuity of 20/70 or better, and 489 (55%) had a visual acuity of 20/40 or better in at least 1 eye. Seventy-five patients (8%) had visual acuity of count fingers or worse in their best eye. There was only one patient with no light perception in each eye. Patients with autosomal dominant RP, as a group, had the least severe and those with X-linked recessive RP had the most severe impairment in visual acuity. Those with autosomal recessive disease were intermediate in severity of visual impairment. CONCLUSIONS Analysis of visual acuity in this large group of patients with RP, which genetically is representative of patients with RP seen in the United States by those who specialize in retinal disease, showed that it was rare for the patients to lose all visual acuity from the disease itself. Further, legal blindness from visual acuity loss, defined as best-corrected visual acuity that is no better than 20/200 in at least one eye, occurred in a relatively small percentage (20%) of our patient population, whereas approximately half of all patients and 42% of those older than 60 years had a visual acuity of 20/40 or better in at least one eye. The extent of impairment in visual acuity was associated with the genetic subtype of the disease.

Light adaptation, rods, and the human cone flicker ERG.

During the course of light adaptation, the amplitude and implicit time of the human cone ERG change systematically. In the present study, the effect of adapting field luminance on these ERG changes was assessed, and the hypothesis that light adaptation of the rod system is the primary determining factor was evaluated. Cone ERG responses, isolated through the use of 31.1-Hz flicker, were obtained from two visually normal subjects, initially under dark-adapted conditions and then repeatedly for 30 min following the onset of each of a series of ganzfeld adapting fields with luminances that ranged from -1.2 to 2.1 log cd/m2. The increase in flicker ERG amplitude and decrease in implicit time during light adaptation were greatest at the highest adapting field luminances. Photopically equivalent achromatic and long-wavelength adapting fields induced comparable increases in flicker ERG amplitude, while scotopically equivalent adapting fields had considerably different effects. This latter finding demonstrates that the rod system is not a major determinant of the adaptation-induced increase in cone ERG amplitude.

Effects of light adaptation on the response characteristics of human oscillatory potentials

We have examined the response characteristics of the oscillatory potentials (OPs) of the human electroretinogram (ERG) obtained to ganzfeld flash stimuli presented against adapting fields. First, we determined the extent to which the OPs obtained to high luminance flashes change during the course of light adaptation to a cone-isolating adapting field. Regardless of the number of OP wavelets, the last OP wavelet increased in amplitude and decreased in implicit time to a greater extent than did the earlier wavelet(s). In addition, we examined the role of both flash and adapting field luminance in determining the wave form of the OPs. For each adapting field luminance that was tested, the number of OP wavelets increased as flash luminance increased, primarily resulting from the splitting of the last OP into 2 distinct wavelets. While the number of OP wavelets generally decreased as adapting field luminance increased, the amplitude of the last OP became larger. These functional distinctions between the last and the earlier wavelets are consistent with their representing the activity of different retinal generators.

Short-term inter-visit variability of erg amplitudes in normal subjects and patients with retinitis pigmentosa.

PURPOSE To evaluate the short-term test/retest variability in visually normal subjects and patients with retinitis pigmentosa (RP), and to assess the effect of stimulus intensity and baseline amplitude on electroretinogram (ERG) variability. METHODS Eighteen patients with RP and nine visually normal subjects had a series of three unilateral ERGs, with an inter-visit interval of no less than 2 days and no more than 2 weeks. Responses to dark-adapted and both light-adapted single flash and 32 Hz flicker stimuli were recorded from a dilated eye over a range of stimulus intensities. B-wave amplitudes were compared to baseline amplitudes recorded at initial visit, and the resulting inter-visit percent difference was compared between stimulus intensities. Inter-visit variability was determined by one-way repeated measures analysis of variance using a 95% confidence interval to calculate threshold criteria for significant change. Analysis of variance followed by Bonferroni test for pairwise comparison was used to test for differences in inter-visit variability between two RP patient subgroups (higher versus lower baseline amplitudes) and visually normal subjects. The effect of stimulus intensity on amplitude reproducibility was also assessed. RESULTS Threshold for significant increase or decrease in inter-visit ERG amplitudes at a 95% confidence level for patients with RP and visually normal subjects was often at or above 25% and not infrequently at or above 40% for certain stimuli and test conditions. While no statistical difference in inter-visit variability was demonstrated between visually normal subjects and patients with RP who were arbitrarily categorized as having relatively higher baseline amplitudes, there was a difference between each of these two groups and a smaller group of patients with RP categorized as having lower baseline amplitudes. Although the authors could not demonstrate that percent inter-visit differences varied with stimulus intensity in either controls or patients with RP, the 32 Hz flicker stimulus generally produced less amplitude variability than either dark- or light-adapted single flash stimuli in patients with RP. CONCLUSIONS When using ERG amplitude for monitoring either the natural history of functional loss in retinal disease or as an outcome measure during a therapeutic trial, it becomes vital to define inter-visit variability of ERG amplitudes. These findings suggest that a percentage of patients with RP with appreciably lower baseline ERG amplitudes may manifest greater inter-visit ERG amplitude variability than patients with RP with higher baseline amplitudes or controls. Stimulus intensity had no clinically significant effect on inter-visit amplitude variability.