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Biomedical subjects

G A Fishman

Publications and source records attributed to G A Fishman.

At least 55 records · Page 3Linked to original sources
PubMed1997

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.

Activities of Daily Living↗
PubMed1997

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.

Half-Life↗
PubMed1997

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.

Adult↗
PubMed1997

Frequency of optic disc or parapapillary nerve fiber layer drusen in retinitis pigmentosa.

PURPOSE: To determine the frequency and characteristics of optic disc and parapapillary nerve fiber layer drusen in patients with retinitis pigmentosa and to attempt to document any differences in the frequency within different genetic subtypes of retinitis pigmentosa. METHODS: This retrospective case series reviewed 117 patients with autosomal-dominant, 84 with autosomal-recessive, and 61 with X-linked recessive forms of retinitis pigmentosa. Color fundus photographs were reviewed independently by three investigators. The presence of optic disc or parapapillary nerve fiber layer drusen was documented only when all three observers concurred as to their presence. The number (isolated or multiple), site (disc, parapapillary, or both), and bilaterality (unilateral or bilateral) were noted in each patient. RESULTS: Optic disc or parapapillary nerve fiber layer drusen or both were observed in 11 patients (9.4%) with autosomal-dominant, 6 patients (7.1%) with autosomal-recessive, and 7 patients (11.5%) with X-linked recessive types of retinitis pigmentosa. The differences in the observed frequencies were not statistically significant (P = 0.67). Overall, the frequency of optic nerve head or parapapillary drusen or both in 262 patients with retinitis pigmentosa was 9.2%. CONCLUSION: In a large population of patients with retinitis pigmentosa, our findings suggest that approximately 10% are likely to show optic nerve fiber layer drusen involving the optic disc or parapapillary regions or both. The frequency does not vary significantly between different genetic subtypes.

Adolescent↗
PubMed1997

Mutations in the cone-rod homeobox gene are associated with the cone-rod dystrophy photoreceptor degeneration.

Crx is a novel paired-like homeodomain protein that is expressed predominantly in retinal photoreceptors and pinealocytes. Its gene has been mapped to chromosome 19q13.3, the site of a disease locus for autosomal dominant cone-rod dystrophy (CORDII). Analysis of the proband from a family with autosomal dominant CORD revealed an Arg41Trp substitution in the third residue of the CRX homeodomain. The sequence change cosegregated with the disease phenotype and was not detected in 247 normal controls. Recombinant CRX homeodomain containing the Arg41Trp substitution showed decreased DNA binding activity. Analysis of another 169 CORD probands identified three additional CRX sequence variations (Arg41Gln, Val242Met, and a 4 bp deletion in codons 196/7) that were not found among the controls. This data suggests that mutations in the CRX gene are associated with photoreceptor degeneration and that the Crx protein is necessary for the maintenance of normal cone and rod function.

Adult↗
PubMed1997

Spectrum of mutations in the RPGR gene that are identified in 20% of families with X-linked retinitis pigmentosa.

The RPGR (retinitis pigmentosa GTPase regulator) gene for RP3, the most frequent genetic subtype of X-linked retinitis pigmentosa (XLRP), has been shown to be mutated in 10%-15% of European XLRP patients. We have examined the RPGR gene for mutations in a cohort of 80 affected males from apparently unrelated XLRP families, by direct sequencing of the PCR-amplified products from the genomic DNA. Fifteen different putative disease-causing mutations were identified in 17 of the 80 families; these include four nonsense mutations, one missense mutation, six microdeletions, and four intronic-sequence substitutions resulting in splice defects. Most of the mutations were detected in the conserved N-terminal region of the RPGR protein, containing tandem repeats homologous to those present in the RCC-1 protein (a guanine nucleotide-exchange factor for Ran-GTPase). Our results indicate that mutations either in as yet uncharacterized sequences of the RPGR gene or in another gene located in its vicinity may be a more frequent cause of XLRP. The reported studies will be beneficial in establishing genotype-phenotype correlations and should lead to further investigations seeking to understand the mechanism of disease pathogenesis.

Carrier Proteins↗
PubMed1997

Reproducibility of visual acuity measurements in patients with retinitis pigmentosa.

PURPOSE: To establish the normal short-term range of variation in the measurement of visual acuity in patients with retinitis pigmentosa. METHODS: Sixteen patients (31 eyes) with retinitis pigmentosa, whose visual acuity ranged from 20/25 to 20/200, participated in this prospective clinical study. The best-corrected visual acuity in undilated and in dilated conditions was recorded independently by two masked observers on two visits of each patient within a 2-week interval by means of the Early Treatment Diabetic Retinopathy Study charts (The Lighthouse, Long Island City, NY). RESULTS: Using mixed-model analysis, a reasonable upperbound for intervisit (intraobserver) variability of 6.0 letters for the visual acuity of patients with undilated pupils and 6.3 letters for the visual acuity of patients with dilated pupils and the corresponding maximum interobserver variability of visual acuity of 5.7 letters in patients with either undilated or dilated pupils on the Early Treatment Diabetic Retinopathy Study charts were computed. The overall average interobserver and intraobserver variability in visual acuity ranged from 1.3-2.3 letters. CONCLUSIONS: A change in visual acuity of seven letters or more on the standardized Early Treatment Diabetic Retinopathy Study charts may be considered important in patients with retinitis pigmentosa. For these patients with minor lens opacity, visual acuity measurements obtained with undilated and dilated pupils were similar. These findings help to establish guidelines for monitoring the response of visual acuity during any future therapeutic intervention trials or for determining substantial changes in visual acuity over time when the course of visual acuity loss in such patients is monitored.

Adult↗
PubMed1997

Efficacy of dorzolamide hydrochloride in the management of chronic cystoid macular edema in patients with retinitis pigmentosa.

PURPOSE: To compare the effectiveness of topical dorzolamide hydrochloride (Trusopt, Merck and Co., Inc., West Point, PA), a carbonic anhydrase inhibitor, with that of oral acetazolamide (Diamox; Lederle Laboratories, Pearl River, NY) for the management of chronic cystoid macular edema in patients with retinitis pigmentosa. METHODS: A prospective, double-masked, crossover study was conducted in five patients with retinitis pigmentosa who had chronic cystoid macular edema. After baseline visual acuity was measured and a fluorescein angiogram was obtained, each patient was randomly assigned to receive either topical dorzolamide or a placebo for 4 weeks, followed by a crossover for the same period. Oral acetazolamide then was given separately to each patient for 2 weeks. Each phase of the study was followed by a washout period of 4 weeks, during which the patient was taken off all medications. At each visit, best corrected visual acuity was measured, a fluorescein angiogram was obtained, a subjective assessment of the effects on visual function, and any side effects of the medication or placebo were recorded in the form of a questionnaire by an independent observer. RESULTS: Compared with baseline or placebo values, there was no measurable improvement in visual acuity on the Early Treatment Diabetic Retinopathy Study charts with dorzolamide in any of the patients. The visual acuity in three of five patients, however, improved by seven letters or more with acetazolamide. Compared again with baseline or placebo values, fluorescein angiograms of two of five patients showed improvement in macular edema in both eyes with the use of dorzolamide, whereas all five showed improvement with acetazolamide. The improvement in macular edema was more marked with acetazolamide than with dorzolamide. The effect of dorzolamide given three times a day was the same as that when it was given five times a day. One patient indicated that dorzolamide was more effective than acetazolamide in improving visual function, three of five patients believed that acetazolamide was more effective, and one felt that both were equally effective. CONCLUSION: Dorzolamide provided improvement in cases of macular edema on fluorescein angiograms and subjective improvement of visual function in some patients with retinitis pigmentosa with cystoid macular edema. However, there was no measurable improvement in visual acuity with the topical use of this drug. Oral acetazolamide was found to be more effective than dorzolamide in managing macular edema and improving visual acuity.

Acetazolamide↗
PubMed1997

Gyrate atrophy-like phenotype with normal plasma ornithine.

PURPOSE: To describe the clinical characteristics of a chorioretinal disease with a gyrate atrophy-like phenotype and normal plasma ornithine. METHODS: One family with three men who had progressive chorioretinal disease and three additional patients with simplex cases were examined clinically and with standard electroretinography, electrooculography, and dark adaptometry. RESULTS: In the family, a 70-year-old man and his two sons (39 and 41 years of age) were affected. On ophthalmoscopy, sharply demarcated peripheral patches of retinal pigment epithelium and choroidal atrophy were seen to progress to the posterior pole in the father's eye. In three unrelated men (62, 70, and 80 years of age), chorioretinal atrophy was present in the mid- and far periphery. Visual acuity was normal in the two youngest of all six patients; however, electroretinogram and electrooculogram waves were reduced. Advanced visual field defects and visual acuity loss occurred in the four older patients. Electroretinogram and electrooculogram were reduced, and the dark adaptation thresholds were elevated. In all patients, serum ornithine levels were normal. Ornithine-delta-aminotransferase activity in cultured skin fibroblasts and the apparent Michaelis constant (Km) for ornithine and alpha-ketoglutarate were within the normal range in all patients. CONCLUSIONS: A gyrate atrophy-like phenotype can result from causes other than deficient ornithine-delta-aminotransferase. Its occurrence in three male members in two generations in one family suggests an autosomal dominant inheritance in at least some such patients.

Adult↗
PubMed1996

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.

Adult↗
PubMed1996

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.

Adolescent↗
PubMed1996

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.

Adult↗
PubMed1996

Frequency of photographically apparent optic disc and parapapillary nerve fiber layer drusen in Usher syndrome.

PURPOSE AND DESIGN: Using a retrospective case series, the authors determine the frequency and clinical features of optic disc and parapapillary nerve fiber layer drusen in type I and type II Usher syndrome (congenital deafness and retinitis pigmentosa). METHODS: Color fundus photographs available on 43 patients with type I and 108 patients with type II Usher syndrome were analyzed for the presence of optic disc or parapapillary nerve fiber layer drusen. RESULTS: Optic disc and/or parapapillary nerve fiber layer drusen were observed in 15 (35%) of 43 patients with type I Usher syndrome and 9 (8%) of 108 patients with type II Usher syndrome for whom color photographs were available. Bilateral drusen were observed in 11 patients (73%) with type I and 3 patients (33%) with type II Usher syndrome. In 3 (20%) of the 15 patients with type I and in 5 (56%) of the 9 patients with type II, only an isolated druse was seen. Six of the 15 patients with type I Usher syndrome showed parapapillary nerve fiber layer drusen, whereas the drusen were within the optic disc in all 9 patients with type II. CONCLUSIONS: Drusen of the optic disc and parapapillary nerve fiber layer tended to occur more frequently in type I than type II Usher patients and also were more often bilateral and multiple, with a tendency to occur in the parapapillary region and within the optic disc.

Adolescent↗
PubMed1995

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.

Adolescent↗
PubMed1995

A comparison of driving in older subjects with and without age-related macular degeneration.

OBJECTIVE: To determine the effects of age and central vision loss on driving skills. METHODS: Ten subjects with age-related macular degeneration and average binocular visual acuity of 20/70, and 11 age-similar subjects with normal vision, were examined with a battery of cognitive and visual tests, an interactive driving simulator, and an on-road driving test. Data were collected on the frequency of real-world accidents and convictions for traffic violations. RESULTS: There were no significant differences between the two groups on any of the cognitive tests. The age-related macular degeneration group demonstrated poorer performance on the driving simulator, including delayed braking response times to stop signs, slower speeds, and more of both lane boundary crossings and simulator accidents. The age-related macular degeneration group also demonstrated poorer overall on-road test performance, including having significantly more points deducted for driving too slowly and for not maintaining proper lane position. However, these effects on the simulator and the on-road test did not translate into an increased risk of real-world accidents for the age-related macular degeneration group. Significantly more control subjects than patients with age-related macular degeneration were involved in self-reported accidents, and significantly more control subjects had state convictions for traffic violations. There was evidence of compensation in the age-related macular degeneration group in four major areas: (1) not driving in unfamiliar areas; (2) traveling at slow speeds; (3) self-restricting their nighttime driving, and (4) taking fewer risks while driving (eg, not changing lanes). There was also evidence of compensation in the older control group. CONCLUSIONS: Vision, simulator, and on-road test variables combined with subjective risk taking predicted self-reported real-world accidents in a logistic regression analysis. However, risk taking, rather than simulator or road-test performance, was the most significant predictor for both patients with age-related macular degeneration and the control group.

Accidents, Traffic↗
PubMed1995

Alex E. Krill: a brief biography of his life and final days.

At the time of his death in 1972 at 44 years, Alex E. Krill had an established reputation as an authority on the topic of inherited retinal and choroidal dystrophies. He lived to see the publication of the first volume of his two volume textbook on Hereditary Retinal and Choroidal Diseases but perished in an airline crash before the completion of the second volume of this text. Although Dr. Krill had completed a substantial portion of the material for this second volume, the publication of a second volume would unlikely have resulted without major additional efforts from two of his colleagues Drs. Desmond Archer, Belfast, Northern Ireland, and August Deutman, Nijmegen, the Netherlands. This work is a testimonial to the scope of Alex Krill's knowledge of various retinal disorders and their proper investigation and classification by electrophysiologic and psychophysical procedures. It is also a lasting tribute to his memory by two generous and devoted colleagues.

History, 20th Century↗
PubMed1995

Granulomatous anterior uveitis presenting with acute posterior multifocal placoid pigment epitheliopathy.

Acute posterior multifocal placoid pigment epitheliopathy (APMPPE) has been described as a posterior segment inflammatory disorder of young adults of unknown etiology. Granulomatous anterior uveitis in association with APMPPE has only rarely been reported in the literature. We report a patient who presented with clinical and angiographic findings consistent with APMPPE in addition to granulomatous anterior uveitis with mutton-fat keratic precipitates and Koeppe nodules. This latter finding has not been emphasized as a possible feature of APMPPE.

Acute Disease↗