Biomedical subjects

G A Fishman

Publications and source records attributed to G A Fishman.

At least 73 records · Page 4Linked to original sources

PubMed1995

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.

Adult↗

PubMed1994

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.

Adolescent↗

PubMed1994

Racial differences in the prevalence of atrophic-appearing macular lesions between black and white patients with retinitis pigmentosa.

We compared the prevalence of atrophic-appearing macular lesions between black and white patients with isolated or various genetic types of retinitis pigmentosa to determine if an appreciable difference existed between these two groups. The study included 720 patients of whom 138 (19.2%) were black patients from 115 families and 582 (80.8%) were white patients from 478 families. A logistic regression analysis combining isolated and all genetic types but randomly selecting one patient per family showed a statistically significant difference in the prevalence of atrophic-appearing macular lesions between black and white patients for the right eye (P = .0012) and left eye (P = .002). When considering either all patients or one patient per family, the estimated odds ratios were approximately 2.0 for blacks relative to whites. Our findings indicate that black patients with retinitis pigmentosa are approximately twice as likely as white patients to develop an atrophic-appearing macular lesion. This observation has implications for the prognosis of central visual function in such patients.

Adolescent↗

PubMed1994

Clinical features of a previously undescribed codon 216 (proline to serine) mutation in the peripherin/retinal degeneration slow gene in autosomal dominant retinitis pigmentosa.

BACKGROUND: Mutations in the human peripherin/retinal degeneration slow (rds) gene have been found in patients with macular dystrophies as well as in those with autosomal dominant retinitis pigmentosa. The authors studied the clinical features in members of two families with autosomal dominant retinitis pigmentosa and a previously unreported mutation in the peripherin/rds gene. METHODS: Affected family members underwent a clinical ophthalmic examination and electrophysiologic and psychophysical testing. Available family members were evaluated for a mutation in the peripherin/rds gene. RESULTS: A mutation in codon 216 of the peripherin/rds gene, resulting in a substitution of the amino acid serine for proline, was found to segregate with retinitis pigmentosa in these two families. Ocular features of this mutation include a later onset of more notable ophthalmoscopic, electrophysiologic, and psychophysical abnormalities of the retina, an atrophic-appearing foveal lesion, and extrafoveal atrophic and hyperpigmented degenerative retinal changes, which were found more posteriorly than usually seen in patients with retinitis pigmentosa. Visual field testing showed a partial ring scotoma or pear-shaped configuration of the remaining portions of the peripheral fields. CONCLUSION: A previously undescribed mutation in the peripherin/rds gene is responsible for an autosomal dominant retinitis pigmentosa phenotype. This phenotype tends to be associated with the development of an atrophic-appearing foveal lesion, more posterior distribution of pigmentary changes involving the vascular arcades, the presence of a partial ring scotoma or a pear-shaped configuration of the peripheral visual field, and a later onset of more extensive retinal structural and functional impairment.

Adolescent↗

PubMed1994

Effect of methazolamide on chronic macular edema in patients with retinitis pigmentosa.

PURPOSE: To determine the effectiveness of methazolamide for improving visual acuity and macular edema in patients with retinitis pigmentosa. METHODS: Seventeen subjects with retinitis pigmentosa and chronic macular edema participated in a prospective, placebo-controlled, double-masked, crossover design study in which either methazolamide or a placebo was taken for 3 weeks. Visual acuity, fluorescein angiograms, and subjective impressions were obtained at baseline and after 3 weeks of treatment with each substance. A subgroup of subjects were enrolled in a more extended period of methazolamide treatment for an additional 3 months. RESULTS: Methazolamide resulted in the improvement of angiographic macular edema in 9 of 17 subjects. As a group, visual acuity statistically improved with methazolamide. However, improvement in at least one eye, of between two and four lines more than while taking placebo, occurred in only three (undilated pupils) or four (dilated pupils) subjects. Subjective improvement during treatment with methazolamide but not placebo occurred in only one subject. An extended period of methazolamide treatment for an additional 3 months in a subgroup of patients did not result in additional beneficial effects on visual acuity. In fact, a partial rebound in the extent of macular edema was found. CONCLUSIONS: Although angiographic improvement of macular edema can occur in patients with retinitis pigmentosa treated with methazolamide, notable (between 3 and 4 lines) or even moderate (between 2 and 3 lines) visual acuity improvement was seen in relatively few patients. When methazolamide was administered in a placebo-controlled fashion, subjective improvement in visual function also was not readily apparent. A more substantial subjective improvement in visual function had occurred with the use of acetazolamide in five of six subjects who also had participated in a previous treatment trial with the use of acetazolamide.

Adolescent↗

PubMed1994

Identification of a gene from Xp21 with similarity to the tctex-1 gene of the murine t complex.

Long range physical mapping within the p21 region of the X chromosome identified a CpG rich island approximately 180 kb centromeric to the chronic granulomatous disease (CGD) locus. The segments adjacent to the CpG island hybridized to discrete bands in DNAs of several species and when used to screen retinal cDNA libraries led to the identification of cDNAs that detected a mRNA of 2.1 kb in many tissues. Molecular characterization of corresponding genomic clones of this novel human gene confirmed the origin of the cDNA clones and indicated a genomic structure with five exons spanning a total of 9 kb. The complete cDNA sequence revealed that this gene contained a putative open reading frame of 116 amino acids with a 3' untranslated region of 1.74 kb. The amino acid sequence shows a high degree of similarity to the predicted product of the tctex-1 gene of the mouse t complex. As linkage studies and patients with deletions have implicated the Xp21 region as containing the retinitis pigmentosa defect (RP3), the gene was assessed as a candidate disease gene in RP3 families. A single base pair polymorphism was identified within the coding region but no disease associated changes were found by single strand conformational polymorphism and sequencing analysis of amplified exons of 20 RP patients. Analysis of a dinucleotide repeat polymorphism within this gene in families affected with RP3 suggested refinement of the RP3 region.

Amino Acid Sequence↗

PubMed1994

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.

Administration, Oral↗

PubMed1994

Dark adaptation in patients with Best vitelliform macular dystrophy.

Psychophysical dark adaptation studies were performed in six patients with Best vitelliform macular dystrophy (BVMD) using a Goldmann-Weekers dark adaptometer. Prebleach thresholds were determined before obtaining a postbleach full recovery curve. Unlike patients with Stargardt macular dystrophy, all patients with BVMD showed a normal time to reach their baseline dark adapted thresholds after bleaching of their rod visual pigment when tested in clinically normal appearing retina. Although a lipofuscin material accumulates within retinal pigment epithelial cells in patients with either Best or Stargardt dystrophy, functional findings pertaining to recovery of rod dark adaptation thresholds as well as electro-oculogram light peak to dark trough ratios are different in these two disorders.

Adolescent↗

PubMed1993

Evaluation of driving performance in patients with juvenile macular dystrophies.

The driving performance of 20 subjects with central vision impairment due to either Stargardt disease or cone-rod dystrophy (visual acuity, 20/40 to 20/70) was compared with that of 29 control subjects with normal vision who had similar driving histories. Driving performance was defined by accident involvement based on self-report and state records and by an evaluation of performance on an interactive driving simulator. The proportion of individuals involved in accidents in the central vision loss group was comparable to that of the control group. For 13 of the 20 subjects with central vision loss who did not restrict their driving to daylight hours, there was a greater likelihood of involvement in nighttime accidents than in the control group. Visual function measures and simulator indexes did not predict accident involvement for the central visual loss group, although these subjects showed longer braking response times and a greater number of lane boundary crossings than the control group. These findings are in contrast to our previously published report of subjects with retinitis pigmentosa, who were more likely to have been involved in both daytime and nighttime accidents than a control group and for whom visual field extent was significantly related to accident involvement.

Accidents, Traffic↗

PubMed1993

Clinical subtypes of cone-rod dystrophy.

OBJECTIVE: To determine possible distinct phenotypic subtypes of cone-rod dystrophy. PATIENTS: Thirty-three patients with cone-rod dystrophy (from 25 families) were assessed prospectively on electroretinography, visual field testing, psychophysical threshold profiles, and fundus features. The clinical records of an additional 150 patients with cone-rod dystrophy were examined retrospectively in terms of the classification schema derived from the prospective study. RESULTS: Based on electroretinographic recordings, two major types of cone-rod dystrophy were differentiated. In type 1, cone amplitudes were reduced to a greater degree than were rod amplitudes on electroretinography, while in type 2, cone and rod electroretinographic amplitudes were reduced in equal proportion. These two types were further subdivided on the basis of patterns of visual field loss and threshold elevation. In type 1a, there was a central or paracentral scotoma, and cone thresholds were more elevated centrally than peripherally. In type 1b, there was no central scotoma, and cone thresholds were more elevated peripherally than centrally. In type 2a, there was a central scotoma, cone thresholds were more elevated centrally than peripherally, and rod thresholds were more elevated peripherally than centrally. In type 2b, a partial or complete ring scotoma was present, cone thresholds were more elevated peripherally than centrally, and rod thresholds were more elevated in the midperipheral than in either the central or far peripheral region of the retina. Of the 150 additional patients with cone-rod dystrophy, data sufficient for classification were available for 95 patients, and all but two had findings that were consistent with classification into one of these four subtypes. CONCLUSION: Our results identify four functionally distinct subtypes of cone-rod dystrophy that may be useful for patient counseling and future molecular genetic studies.

Adolescent↗

PubMed1993

Rebound of macular edema with continued use of methazolamide in patients with retinitis pigmentosa.

PURPOSE: To assess the effect of methazolamide on chronic macular edema in patients with retinitis pigmentosa in a double-masked, placebo-controlled, crossover study. Three subjects who had an initial improvement in their macular edema as demonstrated on fluorescein angiography received a continued course of methazolamide to assess its effect on macular edema. METHODS: Seventeen subjects were enrolled in the initial study. On angiography, nine subjects demonstrated improvement in their macular edema with the use of methazolamide for 3 weeks; three of these continued receiving the drug at a dosage of 50 mg twice daily for either an additional 6 (one subject) or 12 (two subjects) weeks. All subjects were assessed at each visit with fluorescein angiography and on best corrected visual acuity, both undilated and dilated; a subjective impression was also documented. RESULTS: After 6 and 12 weeks of treatment, all three subjects experienced a rebound of angiographic macular edema to some extent. The visual acuity varied only slightly (up to 7 letters) from both the baseline and most recent examinations after 6 and 12 weeks of treatment. CONCLUSION: Results from these few subjects suggest that at least a partial rebound of macular edema seen angiographically may occur with the continued use of methazolamide in patients with retinitis pigmentosa and chronic macular edema. Further study is required to determine if this rebound effect also occurs in treatment of other ocular disorders with chronic macular edema.

Adult↗

PubMed1993

Visual acuity in patients with best vitelliform macular dystrophy.

PURPOSE: Forty-seven patients with Best vitelliform macular dystrophy were evaluated in a cross-sectional fashion for visual acuity loss with age. METHODS: The authors assessed only patients who had at least one eye with a recognizable phenotype of Best vitelliform macular dystrophy. Patients with absent foveal changes or with only minimal foveal pigment mottling and hypopigmentation in each eye were excluded. RESULTS: A significant difference was noted between the visual acuities of the two eyes of the patients (2 lines or greater in the majority [64%] of patients). Nevertheless, for both eyes a significant correlation was noted between patient age and visual acuity, with older patients tending to have worse visual acuities. In the eyes with the best visual acuity, the majority of patients younger than 40 years of age (76%) had a visual acuity of 20/40 or better. In patients older than 30 years of age, a substantial percentage (74%) had a visual acuity of 20/100 or worse in at least one eye. CONCLUSION: The authors' findings indicate that although patients with Best vitelliform macular dystrophy who show characteristic macular lesions may retain good visual acuity in at least one eye, an appreciable number can lose substantial visual acuity, at least monocularly. In this population, no patient older than 50 years of age fulfilled the visual acuity criterion of 20/40 in at least one eye, the requirement in most states for an unrestricted driver's license, and only 20% of patients older than 40 years of age fulfilled this visual acuity criterion.

Adolescent↗

PubMed1993

Polymorphisms and rare sequence variants at the ROM1 locus.

Rom-1 is an integral membrane protein of the rod photoreceptor outer segment. The ROM1 gene is located on human chromosome 11q13, a region to which the loci of four degenerative retinopathies have been mapped. To identify alleles of ROM1, we have screened the DNA of 57 controls and 180 patients with inherited retinopathies. Six ROM1 polymorphisms were identified: two in non-coding sequences (C-7T, T insertion 966/967), two substitutions (Ala118Gly, Arg223Arg), and two RFLPs outside the transcription unit, detected with BcII and Hind III. One rare sequence variant (Arg229His) was found in two adRP probands; in the one family studied the allele was discordant with the disease. A second rare variant (Ala265Thr) was found in both an adRP family and a control; a third rare variant (Met271Thr) was present only in a control family. These polymorphisms will be useful in the evaluation of ROM1 as a candidate gene in inherited retinal diseases. The recognition of the rare variants will prevent their misassignment as disease-causing mutations.

Alleles↗

PubMed1993

Temporal properties of letter identification in retinitis pigmentosa.

The effect of stimulus duration on the visual acuity of individuals with retinitis pigmentosa (RP) was assessed by using Sloan letters of 100% contrast and durations ranging from 15 ms to 3.8 s. In addition, contrast thresholds for identifying Sloan letters (0.7 log minimum angle of resolution; 20/100 Snellen equivalent) were measured over the same range of durations in the same subjects with RP. Compared with results from a control group of subjects with normal vision, the subjects with RP showed losses in visual acuity at all stimulus durations, with a slightly though significantly greater reduction in visual acuity at short durations. The letter-contrast thresholds of the subjects with RP were elevated above the normal range to the same degree at all durations. Analysis of the results in the format of letter contrast sensitivity functions indicates that temporal summation for letter identification was normal for these subjects with RP and that their relatively greater acuity loss at short exposure durations was most likely related to their elevated letter contrast thresholds.

Adult↗

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↗