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Biomedical subjects

Gerald A Fishman

Publications and source records attributed to Gerald A Fishman.

At least 37 records · Page 2Linked to original sources
PubMed2005

Higher-order wavefront aberrations in retinitis pigmentosa.

PURPOSE: The purpose of this study was to characterize higher-order wavefront aberrations associated with posterior subcapsular (PSC) cataracts in patients with retinitis pigmentosa (RP). METHODS: Wavefront aberrations were measured by Shack-Hartmann (SH) aberrometry in eight patients with RP who had PSC cataracts, 10 patients with RP who had minimal or no PSC cataracts, and 16 age-equivalent visually normal control subjects. Higher-order wavefront aberrations for 3-mm and 6-mm pupil diameters were defined as the root mean square (RMS) of the wavefront aberration functions. RESULTS: For a 6-mm pupil diameter, the mean RMS for total higher-order wavefront aberrations was significantly larger for the patients with RP than for the control subjects, both for patients with PSC cataract (F = 17.30, p < 0.001) and for those with minimal or no PSC cataract (F = 4.80, p < 0.05). The mean RMS for third-order aberrations was not significantly different for patients with RP than for the control subjects. However, the mean RMS for fourth-order aberrations was significantly larger for the patients with RP than for the control subjects, both for patients with PSC cataract (F = 8.85, p < 0.01) and those with minimal or no PSC cataract (F = 5.07, p < 0.05). There were no significant differences in higher-order aberrations between the patients with RP and the control subjects for a 3-mm pupil diameter. CONCLUSIONS: Increased higher-order wavefront aberrations were present in patients with RP with and without clinically observable PSC cataracts. The measurement of wavefront aberrations in patients with RP provides an objective and quantitative method for detecting and monitoring disease-related changes in the optics of the eye.

Adult↗
PubMed2005

A method for differentiating ocular higher-order aberrations from light scatter applied to retinitis pigmentosa.

PURPOSE: The purpose of this study is to report a method for differentiating ocular higher-order aberrations and intraocular light scatter based on a deconvolution technique. METHODS: An optical system was used to image a laser slit on the retina and also to perform Shack-Hartmann wavefront sensing. From the laser slit image, the line spread function, incorporating both ocular higher-order aberrations and light scatter, was derived. The laser slit image was deconvolved with a point spread function obtained from the Shack-Hartmann image. The area under the line spread function that was derived from the laser slit image after deconvolution provided a measurement of intraocular light scatter. The deconvolution technique was applied to images obtained in a group of 13 patients (mean age +/- 1 standard deviation: 42 +/- 12 years) with retinitis pigmentosa (RP), a retinal disease in which, by clinical examination, changes in the lens of the eye can be manifested. Measurements were compared with those obtained from 20 visually normal control subjects (mean age +/- 1 standard deviation: 43 +/- 17 years). RESULTS: Combined higher-order aberrations and light scatter, measured as the area under the line spread function derived from the laser slit image, were increased significantly in the patients with RP as compared with the control subjects (p = 0.004). Ocular higher-order aberrations obtained from the Shack-Hartmann images were higher in the patients with RP than in the control subjects (p = 0.05). Intraocular light scatter derived from the deconvolved laser slit image was significantly higher in the patients with RP than in the control subjects (p = 0.009). Minimizing the contribution of ocular higher-order aberrations by deconvolution reduced the area under the line spread function in the control subjects and patients with RP, denoting an improvement in retinal image quality. CONCLUSIONS: A method for differentiating ocular higher-order aberrations and intraocular light scatter based on deconvolution was developed that may be useful for determining the level of improvement in retinal image quality that can be anticipated by the application of adaptive optics to aging and diseased human eyes.

Adult↗
PubMed2005

Eye-movement training for reading in patients with age-related macular degeneration.

PURPOSE: To determine whether training oculomotor control, without direct practice in reading sentences, could increase reading speed in patients with age-related macular degeneration (AMD). METHODS: Sixteen patients with AMD participated in the study (age range, 65-87 years; mean, 77). The training program consisted of a series of exercises that were designed to allow the patients to practice eye movements. At the beginning of training, the subjects practiced small horizontal saccades in response to cognitively easy stimuli (e.g., dots). The training then progressed to practicing larger eye movements and then to practicing saccades with single letters, pairs of letters, and three-letter words. Reading of sentences was practiced in only one exercise, during the last session of the 8-week training. RESULTS: The difference between average reading speeds before and after training was 24.7 wpm (difference between medians, 17.9 wpm). The increase in speed was statistically significant (Wilcoxon signed rank test = 124.0, P < 0.001). There was no significant relationship between change in maximum reading speed and ETDRS (Early Treatment Diabetic Retinopathy Study) acuity (r = -0.14, P = 0.76) or between change in maximum reading speed and age (r = 0.25, P = 0.45). CONCLUSIONS: The results indicate that a training curriculum that concentrates on eye-movement control can increase reading speed in patients with AMD. This finding is especially interesting, because the training involved little direct practice in reading sentences but instead concentrated on having subjects practice control of eye positions and eye movements.

Aged↗
PubMed2005

Contrast response properties of magnocellular and parvocellular pathways in retinitis pigmentosa assessed by the visual evoked potential.

PURPOSE: To evaluate the contrast response of the visual system in retinitis pigmentosa (RP) under conditions designed to emphasize the parvocellular (PC) and magnocellular (MC) pathways. METHOD: Visual evoked potentials (VEPs) were measured in 10 patients with RP and in 10 age-equivalent control subjects with normal visual acuity and color vision, by using an array of isolated checks that were presented against a steady yellow background. The checks were modulated sinusoidally, either in isoluminant chromatic contrast (5.6 Hz), to favor the chromatic PC pathway, or in luminance contrast (5.6 and 11.2 Hz), to favor the MC pathway. Response amplitude and phase at the stimulus (fundamental) frequency were derived from Fourier analysis, and contrast response functions were fit with a Michaelis-Menten equation to derive R(max), the maximum response amplitude, and sigma, the contrast necessary to produce R(max)/2. RESULTS: In the control subjects, the mean amplitude function for chromatic modulation increased approximately linearly with increasing contrast, whereas the function for luminance modulation increased sharply at low contrasts and saturated at contrasts above approximately 30% for both temporal frequencies, as expected. The patients with RP showed primarily a reduction in R(max) with little change in sigma in all testing conditions. The reduction in R(max) was equivalent for chromatic modulation and luminance modulation at 5.6 Hz, but was substantially lower for luminance modulation at 11.2 Hz. CONCLUSION: Contrast processing was impaired within both the MC and PC pathways in these patients with RP, but the degree of impairment within the MC pathway depended on temporal frequency. These VEP results are in general agreement with recent psychophysical studies of contrast sensitivity losses in patients with RP, and further they characterize contrast processing deficits in these patients at suprathreshold levels.

Adult↗
PubMed2004

Novel mutations in the cellular retinaldehyde-binding protein gene (RLBP1) associated with retinitis punctata albescens: evidence of interfamilial genetic heterogeneity and fundus changes in heterozygotes.

OBJECTIVE: To evaluate the molecular genetic defects associated with retinitis punctata albescens (RPA) in 5 patients from 3 families with this disease. METHODS: We examined 3 probands and 2 clinically affected relatives with RPA. Clinical examinations included best-corrected visual acuity, visual field testing, electroretinography, dilated fundus examination, and fundus photography. Leukocyte DNA was analyzed for mutations in the exons of the genes encoding cellular retinaldehyde-binding protein 1 (RLBP1), 11-cis-retinol dehydrogenase (RDH5), interphotoreceptor retinoid-binding protein (RBP3), and photoreceptor all-trans-retinol dehydrogenase (RDH8). Not all patients were evaluated for mutations in each gene. The exons were individually amplified and screened for mutations by single-stranded conformational polymorphism analysis or direct genomic sequencing. RESULTS: The 3 probands had similar clinical findings, including a history of poor night vision, the presence of punctate white deposits in the retina, and substantially reduced or absent rod responses on electroretinogram testing. One of the probands (patient 2:III:2) had 2 novel mutations in the RLBP1 gene (Arg151Trp and Gly31[2-base pair deletion], [GGA-->G-]). Segregation analysis showed that the 2 mutations were allelic and that the patient was a compound heterozygote. Both parents of the proband manifested round white deposits in the retina. The other 2 probands had no detected pathogenic mutations in RLBP1 or in the other 3 genes evaluated. CONCLUSIONS: The identification of novel RLBP1 mutations in 1 of our 3 probands, all with RPA, is further evidence of genetic (nonallelic) heterogeneity in this disease. The presence of round white deposits in the retina may be observed in those heterozygous for RLBP1. Clinical Relevance Patients with a clinical presentation of RPA can have genetically different mutations. Drusen-like lesions may be observed in heterozygotes in families with this disease and a mutation in RLBP1.

Adult↗
PubMed2004

The application of chromatic dark-adapted kinetic perimetry to retinal diseases.

PURPOSE: To demonstrate the value of a 2-color perimetric procedure for determining cone and rod system contributions to the dark-adapted kinetic visual field (VF). DESIGN: Prospective evaluation of perimetric testing procedure. PARTICIPANTS: Five patients with retinal diseases and 6 visually normal individuals. METHODS: Long- and short-wavelength stimuli were presented under dark-adapted conditions in a Goldmann perimeter. Visual fields were measured for the II and V test target sizes with a long-wavelength filter (cut-on at 600 nm) and a short-wavelength filter (cutoff at 510 nm). Light intensities through these filters were matched scotopically for the rod system by producing equal peripheral boundaries on 6 visually normal individuals. To validate the application of this procedure, we tested a patient with congenital achromatopsia and another patient with congenital stationary night blindness (CSNB). We then tested 2 patients with retinitis pigmentosa (RP) and 1 patient with Usher's syndrome to determine the cone and rod contributions to their VF isopters. MAIN OUTCOME MEASURES: Isopters for long- and short-wavelength test stimuli, and the appearance of the test stimuli, whether reported as chromatic or achromatic. RESULTS: The patient with congenital achromatopsia showed superimposed isopters for the 2 stimuli, which were reported as achromatic, demonstrating that the peripheral field boundaries were rod mediated. The patient with CSNB showed an isopter in response to the long-wavelength stimulus that was considerably larger than that in response to the short-wavelength stimulus, both stimuli reported as chromatic, showing that the cone system determined peripheral thresholds for both stimuli. In 2 patients with RP, we observed a mixed pattern of cone or rod system detection of the chromatic stimuli. The peripheral isopters were rod mediated, whereas the cone system determined the central field isopters. In an Usher's syndrome patient, cones mediated both the peripheral and the central field isopters. CONCLUSIONS: A 2-color dark-adapted Goldmann perimetric procedure was able to determine whether the VF isopters were rod or cone mediated in 5 patients with various forms of retinal disease.

Adult↗
PubMed2004

A novel IMPDH1 mutation (Arg231Pro) in a family with a severe form of autosomal dominant retinitis pigmentosa.

PURPOSE: To define ophthalmic findings in a family with autosomal dominant retinitis pigmentosa and a novel IMPDH1 gene mutation. DESIGN: Genetic and observational family study. PARTICIPANTS: Sixteen affected members of a family with autosomal dominant retinitis pigmentosa. METHODS: Ophthalmic examination, including best-corrected visual acuity (VA), slit-lamp biomicroscopy, direct and indirect ophthalmoscopy, Goldmann kinetic perimetry, and electroretinography were performed. Deoxyribonucleic acid single-strand conformation polymorphism (SSCP) analysis was done. Abnormal polymerase chain reaction products identified by SSCP analysis were sequenced bidirectionally. RESULTS: All affected patients had the onset of night blindness within the first decade of life. Ocular findings were characterized by diffuse retinal pigmentary degenerative changes, marked restriction of peripheral visual fields, severe loss of VA, nondetectable electroretinography amplitudes, and a high frequency of posterior subcapsular lens opacities. Affected members were observed to harbor a novel IMPDH1 gene mutation. CONCLUSION: A novel IMPDH1 gene mutation (Arg231Pro) was associated with a severe form of autosomal dominant retinitis pigmentosa. Families affected with a severe form of this genetic subtype should be investigated for a mutation in the IMPDH1 gene.

Adolescent↗
PubMed2004

Monitoring cystoid macular edema by optical coherence tomography in patients with retinitis pigmentosa.

PURPOSE: To determine the value of optical coherence tomography (OCT) imaging in the diagnosis and monitoring of cystoid macular edema (CME) in patients with retinitis pigmentosa (RP). DESIGN: Prospective, noncomparative, small case series. PARTICIPANTS: Three patients with RP and cystic-appearing spaces in the macula on OCT images. INTERVENTION: All 3 patients were treated with a carbonic anhydrase inhibitor, and 1 also received topical and systemic steroids. MAIN OUTCOME MEASURES: Changes in OCT images, fluorescein angiography, and best-corrected visual acuity (VA). RESULTS: Although foveal cysticlike spaces were evident on OCT images in all 3 patients, only 1 patient showed CME on fluorescein angiography at baseline. Two of the 3 patients showed funduscopic evidence of macular cystic lesions, whereas a third showed no clinically evident fundus changes in the macula. Optical coherence tomography images documented improvement in the cystic-appearing spaces after treatment with the carbonic anhydrase inhibitor. Changes on fluorescein angiography were either not apparent or considerably less apparent. An improvement of > or =1 line on a Snellen acuity chart was recorded in 2 patients, whereas a third showed no change of VA in either eye. CONCLUSIONS: Optical coherence tomography is a potential method for the diagnosis and monitoring of CME in patients with RP. It was more sensitive in this regard than either fluorescein angiography or funduscopic examination.

Adolescent↗
PubMed2004

Contrast-processing deficits in melanoma-associated retinopathy.

PURPOSE: To evaluate the hypothesis that patients with melanoma-associated retinopathy (MAR) have a selective functional loss within the magnocellular (MC) pathway of the cone system, with sparing of parvocellular (PC) pathway function. METHODS: Two patients with MAR, ages 57 and 61 years, with normal Snellen visual acuity, participated in the study. Contrast sensitivity was measured at spatial frequencies ranging from 0.25 to 8 cycles per degree (cpd), using two paradigms (steady pedestal and pulsed pedestal) designed to assess the functional integrity of the MC and PC pathways, respectively. Results in patients with MAR were compared with those in 10 visually normal observers, aged 23 to 57 years. RESULTS: Both patients with MAR showed a loss of contrast sensitivity compared to normal observers, but the pattern of loss differed for the two testing paradigms. For the steady-pedestal paradigm (presumed MC-pathway mediation), the patients' sensitivity loss was greatest at the lowest spatial frequency (0.25 cpd) and the sensitivity loss decreased systematically with increasing spatial frequency. For the pulsed-pedestal paradigm (presumed PC-pathway mediation), the sensitivity loss was greatest at an intermediate spatial frequency of 1 cpd. For both paradigms, the patients' sensitivities were within the normal range at the highest spatial frequency (8 cpd), consistent with their normal visual acuity. CONCLUSIONS: The contrast sensitivity deficits of patients with MAR under photopic conditions are not specific to the MC pathway, as proposed previously, but instead are related to the spatial frequency of the test target. The overall pattern of contrast sensitivity loss shown by the patients with MAR is consistent with the dysfunction at the level of the retinal bipolar cells that is presumed to underlie the MAR syndrome.

Adult↗
PubMed2004

Dark adaptation of rod photoreceptors in normal subjects, and in patients with Stargardt disease and an ABCA4 mutation.

PURPOSE: Psychophysical and electroretinographic (ERG) studies indicate that patients with Stargardt disease exhibit abnormally slow rod dark adaptation after illumination that bleaches a substantial fraction of rhodopsin. However, relatively little information is available concerning rod recovery in this disease after weaker adapting (i.e., conditioning) light. With the use of a paired-flash ERG method, properties of the derived rod response to a low-bleach (<1%) but rod-saturating conditioning flash were investigated in seven normal subjects and in five Stargardt patients with identified sequence variations in the ABCA4 gene. METHODS: In the first of two experiments, the interval between a fixed conditioning flash (67 or 670 scotopic cd s m(-2)) and a bright probe flash of fixed strength was varied to determine the falling-phase kinetics of the derived rod response to the conditioning flash. In the second, the instantaneous amplitude-intensity function for the rod response at an intermediate stage of recovery from the conditioning flash was determined by presenting a test flash of various strengths at a fixed time after the conditioning flash, and a probe flash at 200 ms after the test flash. RESULTS: The maximum peak amplitude of the dark-adapted, rod-mediated a-wave determined in Stargardt patients (211 +/- 87 microV) was on average lower than that determined in normal subjects (325 +/- 91 microV; P = 0.06). The derived rod response to the 670 scotopic cd s m(-2) conditioning flash determined in normal subjects and Stargardt patients exhibited a biphasic recovery, and the kinetics of the early stage of this recovery were similar in the two subject groups. For both normal subjects and patients, normalized amplitude-intensity functions describing the dark-adapted derived rod response exhibited half-saturation at approximately 1.5 log scotopic troland second. In both groups, the normalized amplitude-intensity function determined at approximately 2 seconds after the 67 scotopic cd s m(-2) conditioning flash and at approximately 9 seconds after the 670 scotopic cd s m(-2) conditioning flash exhibited an average desensitization (i.e., an increase of test flash strength at half-saturation) of approximately 0.5 to 0.6 log unit relative to that determined under dark-adapted conditions. CONCLUSIONS: The results indicate that, despite a reduction in the average dark-adapted maximum a-wave amplitude in the Stargardt/ABCA4 patients, the early-stage recovery kinetics of the derived rod response to a low-bleaching conditioning flash as well as the lingering rod desensitization produced by such a flash are similar to those determined in normal subjects.

ATP-Binding Cassette Transporters↗
PubMed2004

Contrast sensitivity deficits in inferred magnocellular and parvocellular pathways in retinitis pigmentosa.

PURPOSE: To define the contrast sensitivity deficits of patients with retinitis pigmentosa (RP) under testing conditions designed to emphasize threshold mediation by either the magnocellular (MC) or parvocellular (PC) pathway. METHOD: Contrast sensitivity was measured with spatially localized, narrow-band test patterns at peak spatial frequencies ranging from 0.25 to 8 cycles per degree (cpd), using a steady-pedestal paradigm (brief presentation of the test stimulus against a continuously presented luminance pedestal) and a pulsed-pedestal paradigm (simultaneous brief presentation of the test stimulus and luminance pedestal) to favor the MC and PC pathways, respectively. The contrast sensitivity functions of 12 patients with RP who had visual acuities ranging between 20/12.5 and 20/40 were compared to those of 10 visually normal, age-equivalent control observers. RESULTS: Five of the patients with RP who had Snellen visual acuities better than 20/25 had contrast sensitivity functions that were within the normal limits at all spatial frequencies for both testing paradigms. The other seven patients with RP had reduced contrast sensitivities for both paradigms, with the greatest reduction in sensitivity occurring at the highest spatial frequency. Their contrast sensitivity deficits were equivalent for the steady- and pulsed-pedestal paradigms. CONCLUSIONS: As observed in previous studies, the degree of contrast sensitivity loss shown by the patients with RP was greatest at the highest stimulus spatial frequency. However, in comparison to prior studies of contrast discrimination in patients with RP, there was no evidence of a preferential contrast sensitivity loss within the MC pathway. This apparent discrepancy is attributed to differences in the test targets and psychophysical judgments that were used in the studies, which emphasizes the importance of task characteristics in evaluating relative deficits within the MC and PC processing streams in visual disorders.

Adult↗
PubMed2003

ABCA4 gene sequence variations in patients with autosomal recessive cone-rod dystrophy.

OBJECTIVE: To identify sequence variations in the ABCA4 gene in a cohort of patients with autosomal recessive cone-rod dystrophy. METHODS: The coding sequences of the ABCA4 gene were analyzed in 30 unrelated probands. In those patients with plausible disease-causing variations, correlations were made between genotype and fundus phenotype as well as with electrophysiological and visual field findings. RESULTS: Sixteen (53%) of 30 probands were found to harbor plausible disease-causing variations in the ABCA4 gene. Two distinctly different fundus phenotypes were observed in our cohort of patients. Twelve patients showed diffuse pigmentary degenerative changes, whereas 4 showed either no pigmentary changes or only a mild degree of peripheral pigment degeneration. An associa-tion between certain sequence variations and each of these 2 different phenotypes was observed. CONCLUSIONS: Our findings confirm that a substantial percentage of patients with autosomal recessive cone-rod dystrophy are likely to harbor a mutation in the ABCA4 gene as the cause of their disease. The fundus phenotype observed in such patients is quite variable, and certain fundus phenotypes may be more associated with certain genotypes. Clinical Relevance Identification of the molecular genetic basis for various inherited human retinal dystrophies, such as cone-rod dystrophy, facilitates a potentially better understanding of the mechanisms by which photoreceptor cells degenerate. This in turn provides guidance as to how to better proceed in identifying the most optimal future therapeutic strategies.

ATP-Binding Cassette Transporters↗
PubMed2003

Comparison of the clinical expression of retinitis pigmentosa associated with rhodopsin mutations at codon 347 and codon 23.

PURPOSE: To examine the difference in expression of retinitis pigmentosa from mutations at codon 23 and codon 347 or rhodopsin; to report a novel mutation in rhodopsin. METHODS: Goldmann perimetry (solid angle of I4e isopter) and electroretinographic amplitudes (square root transform of a response ratio) were analyzed for 24 patients with mutations at codon 347 (15 with Pro347Ala, 2 with Pro347Gln, 6 with Pro347Leu, and 1 with a novel Pro347Cys change) and 41 patients with mutations at codon 23 (6 with Pro23Ala; 35 with Pro23His). RESULTS: When all patients with mutations at codons 347 and 23 were compared, loss of visual fields was significantly worse in patients with codon 347 changes (P =.0003). Only rod responses of the electroretinograms were significantly different between the two groups (P =.048). Specific comparison of Pro347Ala with Pro23Ala using regression analysis demonstrated significant differences in severity between codon 23 and codon 347 patients for b-wave amplitudes of rod (P =.0069), cone (P =.039) and maximum combined response (P =.049). The solid angle of the I4e isopter was also significantly different (P =.025) between the groups after controlling for age. Modeling age by group for Pro347Ala comparison produced an R(2) of.44. CONCLUSION: We reconfirmed that rhodopsin-related retinitis pigmentosa from mutations involving codon 347 produces a more severe phenotype than that involving codon 23. Accurate modeling of disease was shown to be possible by incorporating the effects of a patient's age and specific genotype. Therefore, both of these variables must be considered in prognostic counseling and subject recruitment for future therapeutic trials.

Adolescent↗
PubMed2003

Variability of full-field electroretinogram responses in subjects without diffuse photoreceptor cell disease.

PURPOSE: To evaluate test-retest variability in electroretinogram (ERG) responses in subjects without evidence of diffuse photoreceptor cell disease. DESIGN: Cohort study. PARTICIPANTS: Forty subjects without diffuse photoreceptor cell disease. METHODS: Serial ERGs were performed on 40 subjects (mean age at the time of first ERG: 54 years; range: 38-75 years) over a period of 2 to 6 years. These subjects participated in a study by a pharmaceutical company investigating the effects of certain drugs, used for gastrointestinal disorders, on retinal function. None of the subjects showed any evidence of progressive change in retinal function related to the medications. The ERG responses that were evaluated included amplitudes and implicit times for the dark-adapted rod-isolated and rod-dominant responses, light-adapted single flash response, and both light- and dark-adapted 31-Hz flicker responses. MAIN OUTCOME MEASURES: The data were analyzed by using analysis of variance methods, and a threshold criteria for significant change with 95% confidence was calculated for implicit times and an increase or decrease in ERG amplitudes. RESULTS: The threshold for significant change varied depending on the ERG stimulus. For the dark-adapted stimuli, a significant decrease in amplitude varied from 35% to 42% as compared with a variation of 53% to 73% for a significant increase. For the light-adapted stimuli, a significant decrease in amplitude varied by 52% as compared with a variation of 109% to 110% for a significant increase. The threshold for significant change for implicit times varied from 3.0 milliseconds to 8.7 milliseconds. CONCLUSIONS: The measured test-retest variability in ERG amplitudes and implicit times in subjects without diffuse photoreceptor cell disease underscores the importance of conducting similar comprehensive studies of variability in patients with acquired and hereditary retinal diseases. These data are also of value for monitoring disease progression and in future therapeutic trials.

Adult↗
PubMed2003

Visual acuity loss and clinical observations in a large series of patients with Stargardt disease.

PURPOSE: To assess visual acuity impairment in Stargardt disease. DESIGN: Retrospective clinic-based cross-sectional study. PARTICIPANTS: Three-hundred sixty-one patients with Stargardt disease. METHODS: Clinical findings in 361 patients were analyzed as part of a cross-sectional evaluation. Visual acuity at their most recent visit, fundus photographs, and electroretinographic findings were reviewed, and patients were categorized into four clinical phenotypes. Seventy-three patients with 20/40 or better vision and 38 patients with 20/50 to 20/100 vision in the better seeing eye at their initial visit who were followed for at least 1 year were included in a survival analysis. For analysis purposes, these latter patients were categorized into four 20-year age groups according to their age at initial visit. MAIN OUTCOME MEASURES: Best-corrected visual acuity from the eye with better vision on the most recent visit was used in the cross-sectional analysis. For the survival analysis, best-corrected visual acuity was used from the eye with better vision on the initial visit. RESULTS: Eighty-two of the 361 patients (23%) had 20/40 or better acuity in at least one eye, 64 (18%) 20/50 to 20/100, and 199 (55%) 20/200 to 20/400, whereas 16 (4%) had worse than 20/400 in each eye at their most recent visit. In the patients with visual acuity of 20/40 or better, 59 (72%) had foveal sparing visible on ophthalmoscopic examination. The median time to develop visual acuity of 20/200 or worse was 22 years for the patients with 20/40 or better visual acuity at their initial visit. Those seen initially in the first two decades of life with this level of acuity showed a median time of 7 years to reach a visual acuity of 20/200 or worse compared with 22 years and 29 years for those who were initially seen at ages 21 to 40 or 41 to 60, respectively. Analyzing by the four 20-year age groups, the log rank statistic indicated significant differences in the survival experience among the four groups (P = 0.004). The median time to develop 20/200 vision or worse was 6 years for the patients with 20/50 to 20/100 visual acuity at their initial visit, and this result, based on the log rank statistic, was independent of age group at initial visit (P = 0.852). CONCLUSIONS: In a large cohort of Stargardt patients, a cross-sectional analysis showed that almost a quarter had vision of 20/40 or better, whereas 4% had acuity of worse than 20/400. The presence of foveal sparing ophthalmoscopically was associated with a higher prevalence of 20/40 or better visual acuity. Survival analysis showed that the prognosis of patients who initially were seen with visual acuity of 20/40 or better is related to age at initial visit.

Adolescent↗
PubMed2003

Deficits in temporal integration for contrast processing in retinitis pigmentosa.

PURPOSE: The purpose of this study was to evaluate the properties of foveal temporal integration in patients with retinitis pigmentosa (RP) within the framework of contrast processing by the magnocellular (MC) and parvocellular (PC) pathways. METHODS: Temporal integration functions were measured in eight patients with RP whose visual acuities ranged from 20/25 to 20/63. Contrast thresholds were obtained at durations ranging from 15 to 480 ms, using steady-pedestal and pulsed-pedestal paradigms to bias performance toward the MC and PC pathways, respectively. The patients' results were compared with those of 10 age-similar control observers with normal vision. For both paradigms, contrast thresholds as a function of duration were fit with a two-limbed function to derive the critical duration for temporal integration (t(c)) and the asymptotic threshold at long durations (Delta L(infinity)). RESULTS: The log t(c)s of the patients with RP were significantly longer than those of the control subjects for the steady-pedestal paradigm (presumed MC-pathway mediation; t = 3.67, P < 0.001), but not for the pulsed-pedestal paradigm (presumed PC-pathway mediation; t = 0.76, P = 0.45). Further, the patients with RP showed a significant correlation between log t(c) and log Delta L(infinity) for the steady-pedestal paradigm (r = 0.72, P < 0.05) but not for the pulsed-pedestal paradigm (r = -0.37, P = 0.36). CONCLUSIONS: The patients with RP in this study showed greater deficits in contrast sensitivity and a more prolonged critical duration under test conditions that favor the MC rather than the PC pathway. A likely explanation is a high-frequency response attenuation at the level of the cone photoreceptors that has a differential effect on contrast-processing tasks that emphasize different postreceptoral mechanisms.

Adult↗
PubMed2003

ON-pathway dysfunction and timing properties of the flicker ERG in carriers of X-linked retinitis pigmentosa.

PURPOSE: Carriers of X-linked retinitis pigmentosa (XLRP) frequently show prolonged implicit times of the flicker electroretinogram (ERG). This study tested the hypothesis that a preferential response attenuation within the cone depolarizing (ON) bipolar cell (DBC) pathway is a major contributing factor. METHODS: Light-adapted, full-field ERGs were recorded from 10 XLRP carriers and 12 visually normal control subjects. Fundamental amplitudes and phases of ERG responses to sinusoidally flickering stimuli at temporal frequencies ranging from 8 to 96 Hz were analyzed within the framework of a recent vector summation model of the cone system ERG to test for evidence of a response attenuation within the DBC pathway. In addition, ERG responses to sawtooth flicker were examined for a reduced b- to d-wave amplitude ratio, indicative of ON pathway dysfunction. RESULTS: The carriers' fundamental response phases at 32 Hz correlated significantly with their log ratios of response amplitudes at 32 versus 12 Hz (r = 0.89, P < 0.001) and with their log b- to d-wave amplitude ratios (r = 0.71, P < 0.05), both of which were used as indices of response attenuation within the DBC pathway. A control experiment demonstrated that a reduced sensitivity of cone phototransduction made at most only a minimal contribution to the timing changes in the carriers' flicker ERG responses. CONCLUSIONS: The overall pattern of results indicates that a preferential response attenuation within the DBC pathway is the primary source of timing changes in the flicker ERGs of these carriers of XLRP. These findings illustrate the value of analyzing ERG responses to flickering stimuli at multiple temporal frequencies to evaluate mechanisms of disease action in photoreceptor degenerations.

Adolescent↗