Sinclair swine with spontaneously regressing cutaneous melanomas do not have autoantibodies against retinal bipolar cells.
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Animals↗
Biomedical subjects
G A Fishman
Publications and source records attributed to G A Fishman.
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↗
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↗
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↗
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↗
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↗
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↗
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↗
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↗
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↗
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↗
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↗
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↗
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↗
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↗
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↗
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↗
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↗