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Biomedical subjects

G A Fishman

Publications and source records attributed to G A Fishman.

At least 19 recordsLinked to original sources
PubMed1992

Ocular findings associated with rhodopsin gene codon 17 and codon 182 transition mutations in dominant retinitis pigmentosa.

Six members of a family with autosomal dominant retinitis pigmentosa were found to have a cytosine-to-thymine transition mutation in the second nucleotide of codon 17 in the rhodopsin gene that resulted in a threonine to methionine change. Three members from another family with autosomal dominant retinitis pigmentosa showed a guanine-to-adenine transition mutation in the first nucleotide of codon 182 in the rhodopsin gene that resulted in a glycine to serine change. Each of these two mutations presented with a similar phenotype because both showed a regional predilection for pigmentary changes to occur in the inferior part of the retina as well as field impairment predominantly in the superior hemisphere. Electroretinographic amplitudes were more substantial than usually encountered in other forms of retinitis pigmentosa, a finding consistent with the better visual prognosis in patients with either of these two mutations. This article documents the association of two similar phenotypes of autosomal dominant retinitis pigmentosa with specific gene defects at a molecular level.

Adolescent↗
PubMed1992

Ocular findings associated with a rhodopsin gene codon 106 mutation. Glycine-to-arginine change in autosomal dominant retinitis pigmentosa.

Three members of one family and one person from another family were found to have a guanine-to-adenine transition mutation in the first nucleotide of codon 106 in the rhodopsin gene that results in a glycine-to-arginine change. All affected members presented with a similar phenotype that included a regional predilection for pigmentary changes to occur in the inferior retina as well as visual field impairment predominantly in the superior hemisphere. The distribution of pigmentary changes, pattern of visual field loss, and substantial remaining electroretinographic amplitudes with normal implicit times were consistent with a form of "sector" retinitis pigmentosa. We documented the association of a distinct phenotype of autosomal dominant retinitis pigmentosa with a better visual prognosis and a specific rhodopsin gene mutation.

Adult↗
PubMed1992

Ocular findings associated with rhodopsin gene codon 267 and codon 190 mutations in dominant retinitis pigmentosa.

Two members of a family with autosomal dominant retinitis pigmentosa were found to have a cytosine-to-thymine mutation in the second nucleotide of codon 267 in the rhodopsin gene that resulted in a proline-to-leucine change. Two members of another family with autosomal dominant retinitis pigmentosa showed a guanine-to-thymine mutation in the first nucleotide of codon 190 in the rhodopsin gene that resulted in an aspartate-to-tyrosine change. Three members from a third family with autosomal dominant retinitis pigmentosa were also found to have a mutation in codon 190; however, this guanine-to-adenine mutation in the first nucleotide of codon 190 resulted in an aspartate-to-asparagine change. The relatively less severe functional retinal impairment in our patients with a transmembrane codon 267 rhodopsin gene mutation is generally comparable with that observed in a previously described codon 58 transmembrane mutation. The two families with different intradiscal codon 190 mutations showed a considerable difference in severity of their disease.

Adult↗
PubMed1992

Assessment of driving performance in patients with retinitis pigmentosa.

The driving performance of 21 subjects with retinitis pigmentosa (RP) and varying degrees of peripheral field loss was compared with the performance of 31 normally sighted control subjects who did not differ statistically from the subjects with RP in age, gender, years of driving experience, or miles driven per year. Driving performance was assessed by self-reported accident frequency and by an evaluation of performance on an interactive driving simulator. A significantly greater proportion of individuals had self-reported accidents in the RP group than in the normal group. Likewise, a significantly greater proportion of subjects with RP than normal subjects had accidents on the driving simulator. Logistic regression analyses indicated that binocular horizontal field extent and binocular field area significantly differentiated between those having no self-reported accidents and those subjects with RP having one or more self-reported accidents. Because the simulator indexes were correlated with visual field measures for the subjects with RP, no additional information was incorporated into the regression model by adding the simulator measures. Therefore, our results indicate that visual field loss is a primary correlate of automotive accidents in individuals with RP.

Accidents, Traffic↗
PubMed1992

Light adaptation and the luminance-response function of the cone electroretinogram.

Cone electroretinograms are typically isolated by presenting stimulus flashes against rod-desensitizing adapting fields. To investigate the manner in which adapting-field luminance affects cone electroretinogram response properties, we measured cone electroretinogram luminance-response functions of two normal subjects, with stimuli presented against adapting fields that ranged in luminance from -1.2 to 2.1 log cd/m2. A flicker rate of 31.1 Hz was used to isolate cone electroretinograms under all adaptation conditions. A hyperbolic equation of the form (R/Rmax) = Ln/(Ln + Kn) was fitted to each luminance-response function by a least-squares criterion. As adapting field luminance increased, the best-fit values of the variables K and n increased, which is in general agreement with results of electrophysiologic studies of light adaptation in retinal neurons. However, Rmax values also increased with adapting field luminance. The change in all three of these variables with adapting field luminance must be considered in the interpretation of cone electroretinogram luminance-response functions from patients with retinal disorders.

Adaptation, Ocular↗
PubMed1992

Effect of mydriasis on visual field area in retinitis pigmentosa.

PURPOSE: The effect of mydriasis on Goldmann visual field area in patients with retinitis pigmentosa has not been suitably defined. The aim of this study is to determine whether visual field area in these patients varies with pharmacologic mydriasis. METHODS: Fifteen adult patients with retinitis pigmentosa were studied prospectively. Goldmann visual fields with II4e and V4e isopters were obtained in both eyes before and after full pharmacologic mydriasis of the right eye. The isopter areas were quantified and analyzed to determine the effect of mydriasis on visual field area. RESULTS: The difference in the right eye isopter areas was compared with the difference in the left eye isopter areas using paired t tests, where the differences were computed from areas obtained before and after dilation of the right eye. Mydriasis had no significant effect on the visual field in terms of isopter area difference (II4e, P = 0.87; V4e, P = 0.45) and percent change in isopter area (II4e, P = 0.81; V4e, P = 0.24). CONCLUSION: Pharmacologic mydriasis had no appreciable effect on the Goldmann visual field area in a selected group of patients with retinitis pigmentosa. These findings suggest that visual fields of such patients obtained in the dilated or undilated state can be meaningfully compared.

Adult↗
PubMed1992

Dominantly inherited cystoid macular edema. A histopathologic study.

BACKGROUND: Dominantly inherited cystoid macular edema was described as a clinically distinct form of macular dystrophy with an onset at approximately age 30 years with slow progression over the ensuing decades. This is the first report of the light and electron microscopic findings in two donor eyes of one of the patients with this clinical entity. METHODS: Both eyes were obtained after death and fixed within 24 hours in a buffered 4% formaldehyde-1% glutaraldehyde solution. For light microscopy, tissue was embedded in paraffin and stained with hematoxylin-eosin, periodic acid-Schiff, colloidal iron for mucopolysaccharides, and an antibody to glial fibrillar acidic protein. For ultrastructural investigation, several blocks of choroidal/retinal tissues from the posterior pole, including both maculae, were embedded in epoxy resin and processed for transmission electron microscopy. RESULTS: Major findings included large retinal cysts in the macula, atrophy and marked disorganization of the inner nuclear layer, advanced degeneration of Müller cells with nodular aggregates of basement membrane-like material, and a preretinal membrane. The retinal vasculature did not show excessive endothelial alterations but was surrounded by deposits of multilayered basement membrane in the perivascular space. CONCLUSION: The authors believe that the pathologic features of dominantly inherited cystoid macular edema are different from those of macular edema caused by other disease processes. The predominant pathologic changes affected mainly the inner nuclear layer. The possibility of a primary disease of the Müller cell is suggested.

Aged↗
PubMed1992

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.

Adaptation, Ocular↗
PubMed1992

Grating, vernier, and letter acuity in retinitis pigmentosa.

Grating, vernier, and letter acuities were compared in 25 patients with retinitis pigmentosa (RP), whose Snellen visual acuities were better than 20/40, to address the mechanism of visual acuity loss. For these patients with RP, all three types of visual acuity were reduced to an equivalent degree from those of a control group of 10 age-similar, visually normal subjects. The findings indicate that the visual acuity losses of these subjects with RP did not result from cone spatial undersampling (due, for example, to a random loss of foveal cones), from cone sampling irregularities (due to random alterations in foveal cone position), or from a selective loss of sensitivity to high spatial frequencies (as might result from changes in media transmission characteristics or a gain reduction in high spatial frequency mechanisms). In addition, previous studies have indicated that acuity losses in such patients with RP do not result from reductions in the quantum-catching ability of foveal cones. The most likely explanation for the equivalent losses in all three acuity types in these patients with RP appears to be an alteration in foveal spatial scale, consistent with a generalized increase in foveal intercone spacing.

Adult↗
PubMed1992

'On' response defect in paraneoplastic night blindness with cutaneous malignant melanoma.

Response properties of rod and cone systems were assessed in a patient with an acquired form of night blindness associated with a metastatic cutaneous malignant melanoma. The night blindness, a sensation of shimmering lights, and selective reductions in the amplitudes of both rod and cone electroretinographic (ERG) b-waves were present before and after chemotherapy, confirming that this disorder was a paraneoplastic consequence of the melanoma rather than a response to chemotherapy. During ERG testing with flashes of extended duration, the cone b-wave abnormality was found to be a predominant loss of the cone ERG "on" response with relative preservation of the "off" response, similar to that observed in patients with congenital stationary night blindness. An impairment in signal transmission specific for retinal "on" pathways may be a primary defect in both of these forms of night blindness.

Adolescent↗
PubMed1992

Contrast thresholds for letter identification in retinitis pigmentosa.

To assess mechanisms of foveal vision loss in retinitis pigmentosa (RP), contrast thresholds were measured for the identification of Sloan letters at four adapting field luminances (0.4, 1.4, 2.4, and 3.4 log td) in a group of 16 patients with RP who had best-corrected Snellen visual acuities of 20/30 or better, minimal or no posterior subcapsular cataracts, and no atrophic or cystic-appearing foveal lesions. Letter contrast sensitivities of the patients with RP were reduced below those of a group of ten subjects with normal vision for all letter sizes and at all adapting field luminances. The overall pattern of these results indicated that neither a reduced quantal absorption by foveal cones nor spatial undersampling from a loss of foveal cones accounted for the reductions in letter contrast sensitivities. The findings were most consistent with a uniform increase in intercone spacing in the foveas of this group of patients with RP and mild visual acuity loss.

Adaptation, Ocular↗
PubMed1991

Ocular findings associated with a rhodopsin gene codon 58 transversion mutation in autosomal dominant retinitis pigmentosa.

Eight members of a family with autosomal dominant retinitis pigmentosa were found to have a cytosine-to-guanine (C-to-G) transversion mutation in the second nucleotide of codon 58 of the rhodopsin gene, causing a substitution of the amino acid arginine for threonine. Five of these individuals were examined clinically. There was a distinct phenotypic expression of the gene defect within this family that included a regional predilection for pigmentary changes in the inferior and inferonasal parts of the retina, as well as field impairment predominantly in the superior hemisphere. Characteristic electroretinographic recordings and psychophysical threshold profiles also helped to identify this phenotype that, on a relative basis, causes less severe photoreceptor cell functional impairment than often occurs in other subtypes of retinitis pigmentosa. This report documents the association of a clinically recognizable phenotype in a family with autosomal dominant retinitis pigmentosa and a specific gene defect at the molecular level.

Adult↗
PubMed1991

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.

Adult↗
PubMed1991

Effects of chondroitin sulfate on cultured human retinal pigment epithelial cells.

We investigated the effects of chondroitin sulfate on growth, morphology and ultrastructure of retinal pigment epithelial (RPE) cells in culture. When added to the medium, chondroitin sulfate reduced cell density in RPE cultures in a dose-dependent manner. Compared with the controls, the treated cells appeared to be larger and more granular. Electron microscopic examinations revealed accumulations of membrane-bound whorls. In addition, phagocytic activity in the treated cells was notably increased and the level of acid lipase was elevated. These data suggest that increased levels of chondroitin sulfate can induce alterations in both metabolism and activities of RPE cells.

Adult↗
PubMed1991

Regional distribution of retinal degeneration in patients with the proline to histidine mutation in codon 23 of the rhodopsin gene.

Mutations in the rhodopsin gene are associated with as many as one quarter of all cases of autosomal dominant retinitis pigmentosa (RP). A number of different rhodopsin mutations have been reported but only the proline to histidine mutation in codon 23 (Pro-23-His) has been well characterized clinically. One recent report described a "sectoral" distribution of the retinal degeneration associated with this mutation, while another reported only that pigment was present in all four quadrants in 13 of 17 patients. This asymmetric distribution of pigmentation and visual field loss may prove to be an important clinical sign of a type of RP with a relatively good visual prognosis. The authors present a family with Pro-23-His rhodopsin-associated RP in which all six affected individuals had a regional distribution of the retinal degeneration in which the inferior hemisphere of the retina was most severely affected.

Adolescent↗
PubMed1991

Delayed rod dark adaptation in patients with Stargardt's disease.

Twelve patients with Stargardt's dystrophy were each found to have a prolongation in rod dark adaptation. All had a normal rate of recovery during the early portion of rod dark adaptation but a selective prolongation of the later segment of rod recovery. This observation was apparent in patients with limited fundus flecks and those with extensive fundus flecks, whether or not a dark choroid was observed and independent of the presence or absence of an atrophic-appearing macular lesion. A defect within retinal pigment epithelial cells of an enzyme or intracellular transport mechanism involved in the visual pigment regeneration cycle could account for these findings.

Adult↗
PubMed1991

Peripheral vision screening for driving in retinitis pigmentosa patients.

The authors evaluated the test protocols used most frequently to screen the peripheral visual field of driving applicants to determine whether they are suitable for detecting peripheral field loss in patients with retinitis pigmentosa (RP). The peripheral vision tests available on the Keystone View Tester and the Titmus Vision Tester were administered to 23 subjects with RP, 3 subjects with Type 2 Usher's syndrome, and 1 subject who was a partially affected carrier of X-linked recessive RP. The subjects had varying degrees and types of visual field loss. Tests were administered using the standard protocol of the State of Illinois, which is a standard procedure used by state licensing bureaus nationwide. Results demonstrate that the screening protocols use stimulus conditions that are primarily sensitive only to appreciable field losses and examine locations that typically lie within an RP patient's remaining visual field rather than at locations that characteristically are scotomatous. The authors suggest that the current test protocols could determine peripheral field impairment more accurately by assessing additional locations in the visual field, and by introducing a background field and/or by reducing the luminance of the test targets.

Adult↗