Coherence and the judgment of spatial displacements in retinitis pigmentosa.

We used a motion coherence paradigm to test the hypothesis that patients with retinitis pigmentosa (RP) have difficulty discriminating the direction of spatial displacements because of a random loss of motion-sensitive units owing to cone photoreceptor dropout. Minimum (Dmin) and maximum (Dmax) displacement thresholds of patients with typical RP or Usher syndrome were compared with those of age-similar, visually normal subjects. Two-frame random dot cinematograms were used, in which a group of target dots, which comprised 40-100% of the dot array in steps of 20%, were displaced in one of four directions, whereas the non-target dots were randomly repositioned between frames. Reducing the dot coherence in this way increased Dmin and reduced Dmax for both the RP patients and control subjects. Furthermore, the displacement thresholds of the RP patients were displaced laterally from normal along a log coherence axis, consistent with the hypothesis that the patients had a reduced effective (intrinsic) coherence. However, the displacement thresholds of control subjects, when measured at a reduced coherence, did not mimic those of RP patients at full coherence when both groups were tested with a range of dot contrasts and dot areas. These apparently discrepant findings can be reconciled if it is assumed that the patients' effective coherence varies with stimulus visibility.

Variation of clinical expression in patients with Stargardt dystrophy and sequence variations in the ABCR gene.

OBJECTIVE: To report the spectrum of ophthalmic findings in patients with Stargardt dystrophy or fundus flavimaculatus who have a specific sequence variation in the ABCR gene. PATIENTS: Twenty-nine patients with Stargardt dystrophy or fundus flavimaculatus from different pedigrees were identified with possible disease-causing sequence variations in the ABCR gene from a group of 66 patients who were screened for sequence variations in this gene. METHODS: Patients underwent a routine ocular examination, including slitlamp biomicroscopy and a dilated fundus examination. Fluorescein angiography was performed on 22 patients, and electroretinographic measurements were obtained on 24 of 29 patients. Kinetic visual fields were measured with a Goldmann perimeter in 26 patients. Single-strand conformation polymorphism analysis and DNA sequencing were used to identify variations in coding sequences of the ABCR gene. RESULTS: Three clinical phenotypes were observed among these 29 patients. In phenotype I, 9 of 12 patients had a sequence change in exon 42 of the ABCR gene in which the amino acid glutamic acid was substituted for glycine (Gly1961Glu). In only 4 of these 9 patients was a second possible disease-causing mutation found on the other ABCR allele. In addition to an atrophic-appearing macular lesion, phenotype I was characterized by localized perifoveal yellowish white flecks, the absence of a dark choroid, and normal electroretinographic amplitudes. Phenotype II consisted of 10 patients who showed a dark choroid and more diffuse yellowish white flecks in the fundus. None exhibited the Gly1961Glu change. Phenotype III consisted of 7 patients who showed extensive atrophic-appearing changes of the retinal pigment epithelium. Electroretinographic cone and rod amplitudes were reduced. One patient showed the Gly1961Glu change. CONCLUSIONS: A wide variation in clinical phenotype can occur in patients with sequence changes in the ABCR gene. In individual patients, a certain phenotype seems to be associated with the presence of a Gly1961Glu change in exon 42 of the ABCR gene. CLINICAL RELEVANCE: The identification of correlations between specific mutations in the ABCR gene and clinical phenotypes will better facilitate the counseling of patients on their visual prognosis. This information will also likely be important for future therapeutic trials in patients with Stargardt dystrophy.

X-linked retinitis pigmentosa in two families with a missense mutation in the RPGR gene and putative change of glycine to valine at codon 60.

OBJECTIVE: This study describes the ophthalmic findings in two unrelated white families with X-linked retinitis pigmentosa (XLRP) caused by a missense mutation in the retinitis pigmentosa GTPase regulator (RPGR) gene. DESIGN: Genetic screening and clinical correlation. PARTICIPANTS: Thirty-six families with XLRP seen by the authors were screened for a possible mutation in the RPGR gene to identify three affected hemizygotes with retinitis pigmentosa and four heterozygote carriers in one family and one hemizygote and one carrier in a second family. INTERVENTION: All nine patients underwent a routine ocular examination, including slit-lamp biomicroscopy and a dilated fundus examination. Goldmann visual field kinetic perimetry, static threshold perimetry, and electroretinography also were obtained. The DNA screening was performed on the three affected male patients and four obligate carriers examined from one family and the two examined patients, plus an additional male and obligate carrier, from the second family to determine the presence of any causative mutation in the RPGR gene. MAIN OUTCOME MEASURES: Findings on fundus examination, static threshold and kinetic perimetry, and electroretinography testing were the main outcome measures. RESULTS: A G-->T nucleotide change at position 238 in exon 3 of the RPGR gene resulting in a putative substitute of Gly-->Val at codon 60 was shown to segregate with RP in affected males and the carrier state in female heterozygotes in these two families. The ophthalmologic findings in hemizygotes as well as the carriers in this family were within the spectrum of findings characteristically noted in XLRP families. A tapetal-like reflex was not observed in any of the five female carriers. Psychophysical and electrophysiologic testing on the carriers indicated that cone and rod functions were impaired equivalently. When present in the carriers, visual field restriction was most apparent in, or limited to, the superotemporal quadrant, which corresponded to the retinal pigmentary changes that tended to occur in the inferonasal retina. CONCLUSIONS: A mutation in exon 3 of the RPGR gene, which would result in a putative glycine to valine substitution at codon 60, is associated with a severe clinical phenotype in male patients and a patchy retinopathy without a tapetal-like reflex in carrier females. In these families, heterozygote carriers showed equivalent impairment of their cone and rod function.

Effect of noise contrast polarity and temporal asynchrony on visual sensitivity.

We evaluated the effect of substitutive noise on contrast sensitivity within the context of linear (Fourier) and nonlinear (non-Fourier) visual processes. Orientation judgments for D6 (sixth spatial derivative of Gaussian) patterns were obtained from three visually normal subjects when random regions of the target and background were occluded by small (1.7 arc min) pixel arrays that were either all of the same contrast polarity or a mixture of equal percentages of negative and positive contrast. The target was presented either synchronously or asynchronously with the occluding elements. Our results indicate that the manipulation of noise characteristics in this way can bias performance either toward a nonlinear process that is insensitive to noise contrast polarity but sensitive to temporal asynchrony or toward a quasi-linear process that is sensitive to noise contrast polarity but insensitive to temporal asynchrony. These findings have relevance to models of the effect of spatial sampling on the visual performance of persons with retinal disease.

Discrimination of spatial displacements by patients with retinitis pigmentosa.

We compared maximum displacement thresholds (Dmax) with minimum displacement thresholds (Dmin) in patients with retinitis pigmentosa (RP) in order to characterize the nature of their visual disability, as well as to assess possible models of foveal vision loss. Thresholds for discriminating the direction of the spatial displacement of random dot patterns were measured in a group of 20 patients with typical RP or Usher syndrome whose visual acuities were 20/40 or better and who had minimal or no clinical evidence of changes in the ocular media. Findings were compared with those from an age-similar group of 15 visually normal subjects. Displacement thresholds were measured using a two-frame random dot cinematogram and a four-alternative forced-choice procedure. Measurements were made at each of three dot contrasts and three dot sizes. For the patients with RP, reducing either the dot contrast or dot size increased Dmin and decreased Dmax such that the range of discriminable displacements became considerably restricted, even at modest reductions in dot contrast or size. This restriction in the displacement thresholds of the patients with RP was correlated significantly with their visual acuity. By comparison, the control subjects showed little change in either Dmin or Dmax under these conditions. These results indicate that patients with RP who have only relatively minor reductions in their visual acuity can have severely compromised motion perception. The pattern of findings suggests that an abnormal contrast response of the foveal cone system is a major determinant of the impaired displacement thresholds of these patients with RP.

Visual acuity and visual field impairment in Usher syndrome.

OBJECTIVE: To determine the extent of visual acuity and visual field impairment in patients with types 1 and 2 Usher syndrome. METHODS: The records of 53 patients with type 1 and 120 patients with type 2 Usher syndrome were reviewed for visual acuity and visual field area at their most recent visit. Visual field areas were determined by planimetry of the II4e and V4e isopters obtained with a Goldmann perimeter. Both ordinary and logistic regression models were used to evaluate differences in visual acuity and visual field impairment between patients with type 1 and type 2 Usher syndrome. RESULTS: The difference in visual acuity of the better eye between patients with type 1 and type 2 varied by patient age (P=.01, based on a multiple regression model). The maximum difference in visual acuity between the 2 groups occurred during the third and fourth decades of life (with the type 1 patients being more impaired), while more similar acuities were seen in both younger and older patients. Fifty-one percent (n=27) of the type 1 patients had a visual acuity of 20/40 or better in at least 1 eye compared with 72% (n=87) of the type 2 patients (age-adjusted odds ratio, 3.9). Visual field area to both the II4e (P=.001) and V4e (P<.001) targets was more impaired in the better eye of type 1 patients than type 2 patients. A concentric central visual field greater than 20 degrees in at least 1 eye was present in 20 (59%) of the available 34 visual fields of type 1 patients compared with 70 (67%) of the available 104 visual fields of type 2 patients (age-adjusted odds ratio, 2.9) with the V4e target and in 6 (21%) of the available 29 visual fields of type 1 patients compared with 36 (38%) of the available 94 visual fields of type 2 patients (age-adjusted odds ratio, 4.9) with the II4e target. The fraction of patients who had a visual acuity of 20/40 or better and a concentric central visual field greater than 20 degrees to the II4e target in at least 1 eye was 17% (n=5) in the type 1 patients and 35% (n=33) in the type 2 patients (age-adjusted odds ratio, 3.9). CONCLUSIONS: Visual acuity and visual field area were more impaired in patients with type 1 than type 2 Usher syndrome. Of note, 27 of 53 type 1 (51%) and 87 of 120 type 2 (72%) patients had a visual acuity of 20/40 or better in at least 1 eye. These data are useful for overall counseling of patients with Usher syndrome.

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 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.

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.

Serine-27-phenylalanine mutation within the peripherin/RDS gene in a family with cone dystrophy.

PURPOSE: To evaluate the clinical and electrophysiologic findings in a family with two heterozygous sequence changes in the peripherin-retinal degeneration slow (RDS) gene. METHODS: A family study was done of a pedigree obtained by screening for rhodopsin, peripherin/RDS, or rom-1 gene mutations in probands from families with hereditary retinal diseases. The patients consisted of three affected and four unaffected members from a family with cone dystrophy. Ophthalmoscopy, visual field testing, electroretinography, and DNA analysis were performed. RESULTS: Denaturing gradient gel electrophoresis showed the presence of two different sequence changes in the RDS genes of this family. In three members with a retinal disease, the authors observed the substitution of phenylalanine for serine in codon 27 (serine-27-phenylalanine). The clinical and functional findings in these three patients were most consistent with autosomal-dominant cone dystrophy. Three other family members, unaffected with retinal disease, were found to show a substitution of serine for cysteine in codon 72 of the peripherin protein. CONCLUSION: A peripherin/RDS sequence change may produce a cone dystrophy with minimal ophthalmoscopic changes in the macula and limited peripheral degenerative changes. Caution is warranted to avoid ascribing nondisease-causing sequence polymorphisms in candidate genes as responsible for determining the development of a retinal disease phenotype.

Relationship between difficulty in performing daily activities and clinical measures of visual function in patients with retinitis pigmentosa.

OBJECTIVES: To assess the level of perceived difficulty experienced by patients with retinitis pigmentosa (RP) in the performance of everyday activities and to determine the correlation between patients' self-reported difficulty and clinical measures of visual function. METHODS: One hundred sixty-seven patients with typical RP and Usher syndrome type 2, with a wide range of disease severity, rated their difficulty in the performance of 33 activities. We obtained data on visual acuity and visual field area for all patients, and electroretinogram (ERG) recordings on a subgroup of 49 of these patients. Results from the questionnaire were analyzed with factor analysis, and patients' self-reports were compared with their clinical data using correlational analyses and multiple regression. RESULTS: The patients' questionnaire responses clustered into 6 factors: activities involving central vision, miscellaneous activities (no discernible common factor), activities related to mobility, driving, negotiating steps, and eating meals. Of the clinical tests, visual acuity was most strongly related to the patients' ratings of their difficulty in performance. Visual field area also was related to patients' self-assessments but not as strongly as visual acuity. Because visual field area and the ERG measures were correlated, adding ERG information did not improve predictability. CONCLUSIONS: In patients with RP, perceived difficulty in performing common tasks was most strongly related to level of visual acuity and visual fields. Although certain ERG amplitude measures did show positive correlations with some self-reported activities, overall, the ERG amplitude measures showed the least relationship with patients' self-reports. Our results provide insight into RP patients' perceived difficulties in performing everyday activities and the clinical measures of visual function that most highly correlate with these difficulties.

Intraocular light scatter in patients with retinitis pigmentosa.

We evaluated the level of intraocular light scatter in a group of patients with retinitis pigmentosa (RP) who had minimal or no lens opacities, since such patients not infrequently complain of photoaversion. Intraocular light scatter was measured in 20 patients with RP who were < 60 years of age and who had no more than a trace of posterior subcapsular (PSC) lens opacity by slit-lamp evaluation. Measurements of intraocular straylight were made using a van den Berg Straylightmeter. Results from the patients with RP were compared with those of a control group of 30 subjects with normal vision whose ages were similar to those of the patients with RP. Seventeen of the 20 patients with RP had straylight levels that were above the range of age-similar normal control subjects. In some patients, the straylight parameter was increased by a factor of 2.5 above the normal mean for the patient's age and by as much as four to five times the normal mean for 20-yr-old subjects. There was a statistically significant correlation (r = -0.73, P < 0.01) between the patients' log relative elevation in the straylight parameter and their log visual field areas. Our findings indicate that patients with RP can have increased levels of intraocular light scatter despite minimal or no clinically observable PSC lens opacities. The increased intraocular straylight, which is likely due at least in part to subclinical abnormalities in lens morphology, can accentuate the visual disability of patients with RP in the presence of glare sources.

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.

Acquired unilateral night blindness associated with a negative electroretinogram waveform.

PURPOSE: The authors performed clinical, electrophysiologic, psychophysical, and immunologic studies in a patient who presented with an acquired night blindness in one eye to better define the clinical and functional changes in this rare disorder. METHODS: In addition to an ophthalmologic examination, the patient underwent the measurement of electroretinogram responses, dark-adapted thresholds using a Tübingen perimeter (Oculus, Tubingen, Germany), color vision assessment, kinetic visual-field testing using a Goldman perimeter, and immunologic testing to determine if the serum contained autoantibodies to retinal bipolar cells. RESULTS: Fundus examination showed no clinically apparent abnormality in either eye. The patient showed a selective reduction in the b-wave amplitude of the rod electroretinogram and an abnormality of the cone electroretinogram ON response in the affected left eye, whereas the rod and cone electroretinograms of the right eye were normal. Rod thresholds in the affected eye were elevated markedly, whereas rod thresholds in the right eye were normal centrally and slightly elevated in the far periphery. Immunologic testing did not show circulating autoantibodies to retinal cells. CONCLUSIONS: The patient examined in this study showed phenotypic similarities to patients with congenital stationary night blindness and to patients with an acquired form of night blindness associated with cutaneous melanoma (MAR syndrome). The electroretinogram findings from the patient are consistent with an acquired defect in signal transmission from photoreceptors to ON-type bipolar cells. However, the etiology of this unique form of unilateral night blindness remains obscure.

Effect of spatial sampling on grating resolution and letter identification.

The purpose of the study was to determine whether spatial sampling has equivalent effects on visual performance for grating and letter stimuli, two optotypes that are frequently used in the clinical assessment of visual function. Test targets consisted of five-bar square-wave gratings, spatial D6 (sixth derivative of a Gaussian) patterns, or individual Sloan letters, presented for 255 ms in the center of an adapting field. Spatial sampling was introduced by replacing random regions of the targets with occluding elements that had the same luminance as the adapting field, so that only random samples of the test target were visible on each trial. The occluding elements consisted of 4 x 4, 8 x 8, or 16 x 16 pixel arrays (subtending 0.67, 1.33, and 2.67 arcmin, respectively), and the percentage of the test target that remained unoccluded ranged from 3% to 100%. Visual acuity and contrast sensitivity for the spatially sampled targets were measured in two visually normal subjects. Results were compared with the predicted effect of the reduction in effective contrast that was introduced by the sampling paradigm. For grating stimuli the effect of spatial sampling was equivalent to the reduction in effective stimulus contrast produced by the sampling, regardless of occluding-element size. For letter stimuli the reduction in effective stimulus contrast predicted most, but not all, of the loss of visual acuity and contrast sensitivity for sampled targets, and the deficit in performance increased when larger occluding elements were used.(ABSTRACT TRUNCATED AT 250 WORDS)

Prevalence of foveal lesions in type 1 and type 2 Usher's syndrome.

PURPOSE: To evaluate possible differences in the prevalence of clinically detectable foveal lesions between patients with type 1 and type 2 Usher's syndrome. METHODS: Records of 48 patients with type 1 and 98 patients with type 2 Usher's syndrome were retrospectively evaluated for the presence of a foveal lesion. The age, gender, and racial distribution of patients were similar in the two subtypes. Two investigators reviewed fundus photographs from all patients and, when available, fluorescein angiograms. RESULTS: In the 48 patients with type 1 Usher's syndrome, 30 (62%) showed a clinically apparent atrophic- or cystic-appearing foveal lesion, whereas in the 98 patients with type 2 Usher's syndrome, 33 (34%) had either an atrophic- or a cystic-appearing foveal lesion. Logistic regression analysis showed that the probability of exhibiting a foveal lesion in both type 1 and type 2 Usher's syndrome increases with age and that patients with type 1 Usher's syndrome are more likely to have a foveal lesion than are patients with type 2 Usher's syndrome. CONCLUSIONS: Patients with type 1 Usher's syndrome show a greater probability of having either an atrophic- or cystic-appearing foveal lesion than do patients with type 2 Usher's syndrome. This higher prevalence of foveal lesions is consistent with a previous observation that the severity of visual acuity impairment with age is greater for patients with type 1 than type 2 Usher's syndrome. These data are useful in counseling such patients as to their prognosis for central visual function.

Visual acuity vs letter contrast sensitivity in retinitis pigmentosa.

This study examined the quantitative relationship between foveal visual acuity and contrast sensitivity for large-letter optotypes in a group of patients with retinitis pigmentosa (RP), in order to assess more completely the extent of foveal vision loss in this group of hereditary retinal dystrophies. High-contrast visual acuity and large-letter contrast sensitivity were measured with a computer-based testing system and with commercially available letter charts (Lighthouse Distance Visual Acuity Test; Pelli-Robson Contrast Sensitivity Chart). Findings from 20 patients with typical RP or Usher syndrome were compared with those from 15 age-similar control subjects with normal vision. On both the computer-based test and the chart tests, the patients with RP showed approximately equal reductions in visual acuity and large-letter contrast sensitivity. However, intersubject controls was greater for contrast sensitivity than for visual acuity on both test protocols. As a result, the patients with RP required a greater reduction in contrast sensitivity than in acuity to exceed the normal range, indicating that visual acuity was the more sensitive index of the loss of foveal visual function.

Prolonged rod dark adaptation in patients with cone-rod dystrophy.

Thirteen patients with cone-rod dystrophy were assigned into one of four previously described category subtypes according to clinical, electrophysiologic, and psychophysical criteria. The time course of rod dark adaptation was determined for each patient by means of a Goldmann-Weekers dark adaptometer. Nine of the 13 patients showed a normal time to return to their dark-adapted thresholds before bleaching, while four patients showed a prolonged recovery time. The four patients with a prolonged rod-recovery time were all from the same clinical subtype and showed a similar fundus appearance as well as similar electrophysiologic and psychophysical findings.

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.

Effect of vitamin A treatment on the prolongation of dark adaptation in Stargardt's dystrophy.

BACKGROUND: Prolongation in recovery of rod thresholds has been demonstrated in Stargardt's dystrophy. One possible explanation for this finding includes an impairment of vitamin A transport by the retinal pigment epithelium (RPE). By delivering an increased amount of vitamin A to the RPE, it might be possible to overcome a relative deficiency of vitamin A utilization or transport, and thus improve rod dark adaptation. METHODS: Baseline dark-adapted rod final thresholds were measured for five patients with Stargardt's dystrophy after 60 minutes of dark adaptation. A full dark-adaptation curve was then measured after exposure to a bleaching light for 5 minutes. Time of recovery to within 0.2 log units of the prebleach dark-adapted rod threshold was determined. Each subject then took a 14- to 18-day course of oral vitamin A, 50,000 IU daily. Dark adaptation was then reassessed using the same pretreatment protocol. RESULTS: Before treatment, all five patients had a prolongation of their rod recovery curve. There was no statistically significant difference between subjects in mean time taken to reach prebleach rod baseline thresholds before and after vitamin A treatment. CONCLUSIONS: These findings do not rule out the possibility that a delay in rod dark adaptation in Stargardt's dystrophy results from an inability to transport vitamin A from the RPE to photoreceptor cells. Nevertheless, a high dose of oral vitamin A taken for at least 14 days did not provide any objective improvement in dark-adaptation function in five such patients.