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Visual pigment gene changes in adrenoleukodystrophy.

PURPOSE: The gene for X-linked adrenoleukodystrophy, a neurodegenerative disorder, is closely linked to the red/green color pigment genes on the distal X-chromosome Xq28 and one kindred is known to have a genetic change affecting both loci. The purpose of this article is to perform a systematic assessment of the frequency of this situation in many affected kindreds. METHODS: Recombinant DNA probes were used in blot hybridization studies to determine the structure of the color pigment genes in affected males from 59 different adrenoleukodystrophy kindreds. Whenever possible, color vision was measured using the Farnsworth 100-Hue test. RESULTS: Eleven of the 59 kindreds had abnormal color pigment gene clusters; these included fusion genes and changes in gene number. Only one kindred had a deletion of sequences immediately 5' to the color pigment genes. CONCLUSIONS: The incidence of color pigment gene changes in our 59 adrenoleukodystrophy kindreds is approximately twice the frequency of defective color vision reported in historic studies but is about the same as that found in studies of the actual genes in large populations. However, the range of changes in the color pigment genes in adrenoleukodystrophy is broader than encountered in most populations. Changes in the highly conserved color pigment genes reflect reorganizations in the Xq28 chromosomal region, some of which involve the contiguous gene for adrenoleukodystrophy.

Adrenoleukodystrophy↗

Electrophysiological estimation of the function of different retinal zones in normal eyes and in retinal degenerations.

By means of electroretinographical responses from different areas of the retina (zonular ERGs) both healthy people and patients with central and peripheral retinal degenerations were examined. Responses were registered from three retinal areas (zones): central (red, green, and blue stimuli, 10 degrees in diameter, during adaptation of 20 lux); paramacular (a dim, blue, ringlike stimulus, 15 degrees inner and 50 degrees outer diameter, presented at the beginning of dark adaptation) and peripheral (very dim, blue ring stimulus of a 50 degree inner and 110 degrees outer diameter, after 3 min of dark adaptation). The data obtained by this method of stimulation give information about the function of stimulated retinal areas and provide new criteria for the function of the spectrally different photoreceptors responsible for intact color vision. Examples are presented that reveal the value of this method for the detection of congenital color vision defects and for the classification of different types of retinal degeneration. This method is shown to be highly effective and has many advantages over the common routine Ganzfeld ERG technique, especially in cases of unusual retinal degenerations.

Color↗

Chromograms of color normals and multiple sclerosis patients.

The Gunkel chromograph was tested on 81 volunteers with normal color vision as indicated by screening with Ishihara plates and the panel D-15. Most of these color normals located their neutral area superior to the geometric center of the chromogram. A minority located their neutral area at the geometric center. Recognition of this variation may prevent misdiagnosis of chromographs of patients suspected of having color vision defects. All 29 eyes with history and VEP findings consistent with optic nerve demyelinization had enlargement of the neutral area, even though visual acuity could be corrected to 20/20.

Adolescent↗

[Progressive cone dystrophy: electrophysiological changes in female carriers].

The authors evaluated a family with X-linked progressive cone dystrophy and special attention was paid to female carriers. Twenty-four members of the family were examined. One generation II--male and five generation III--males were affected. Two generation II--females who, in each case had affected children, but who were asymptomatic, underwent electrophysiological evaluations. The electroretinograms were found to be subnormal in both patients with alterations of cone-mediated responses and color vision. The discovery of abnormalities in female carriers emphasized the necessity of systematically performing electroretinography, together with color vision testing and pedigree examination, when assessing so called sporadic cone dystrophy or in cases where the modes of inheritance are not clear.

Adolescent↗

Clinical heterogeneity in autosomal dominant optic atrophy in two 3q28-qter linked central Illinois families.

PURPOSE: To examine the clinical and genetic heterogeneity of autosomal dominant optic atrophy among two unrelated central Illinois families. METHODS: Forty-three individuals from two pedigrees had complete eye examinations. Linkage analysis was performed with microsatellite markers from the region 3q28-29. RESULTS: Visual acuity in 21 affected individuals ranged from 20/25 to 20/800. Vision loss was more severe in males than females (P = 0.02). Color vision testing revealed generalized dyschromatopsia. Both visual acuity and color vision deteriorated with age. Linkage was established to chromosome 3q28-29 (LODmax = 4.68 for D3S2305). CONCLUSION: Autosomal dominant optic atrophy linked to chromosome 3q28-29 shows intrafamilial phenotypic variation as well as sex-influenced severity in two Midwestern families.

Adolescent↗

[Treatment of Grave's ophthalmopathy with high doses of corticosteroids].

UNLABELLED: Severe ophthalmopathy with sight impairment and double vision due to a compressive optic neuropathy, extraocular muscle thickness and corneal exposure occurs in 3-5% of all patients with Graves' hyperthyroidism [1]. Steroids are the choice of treatment for ophthalmopathy in more than 50%, and with orbital radiotherapy or surgical decompression in more than 70% of cases [2]. In severe ophthalmopathy steroids are effective in more than 60% of patients [1, 3], but to be effective high dosage is necessary [1, 4-6]. High-dose intravenous steroid pulse therapy is probably preferable to oral steroids giving a better response with fewer adverse effects [6]. The aim of the study was to evaluate the efficacy of high-dose intravenous methylprednisolone pulse therapy followed by oral steroids in the treatment of patients with severe Graves' ophthalmopathy. PATIENTS AND METHODS: Fourteen euthyroid patients with severe Graves' ophthalmopathy were treated with high-dose intravenous methylprednisolone during 6 months and followed-up for 24-48 months by clinical and ophthalmological assessment. During three days two doses of methylprednisolone were given as 500 mg in 500 ml isotonic saline infusion. The treatment was followed by oral prednisone 40 mg daily and tapered off to 10 mg in four weeks when next course of therapy started. There were no contraindications for steroid treatment. Characteristics of the group are presented in Table 1. Ophthalmological assessment relating to the status of cornea, extraocular muscles, eyelids, proptosis and optic nerve function was done during the study. It provides the measurement of visual acuity, intraocular pressure, visual evoked potentials, palpebral apertures and proptosis, fundoscopy, the assessment of ocular motility, visual fields, color vision, lagophthalmos and corneal changes. For better evaluation of eye disease clinical activity score and patients self-assessment were used. Thyroid hormones and thyroid microsomal antibodies were measured during the study. All patients were photographed before and after treatment. Orbital computed tomograms were performed before and after treatment for extraocular muscles assessment. Data were analyzed by Wilcoxon test. RESULTS: Clinical activity score fell significantly within the first week of therapy in all patients and remained stable during the follow-up period (before treatment: mediana 5, min 3, max 7 and after: mediana 2, min 1, max 4, p < 0.01). Proptosis (Table 2, Figure 1) was significantly reduced (mean values before and after treatment were 24.15 mm and 22.75 mm respectively, the difference was 1.40 mm; p = 0.014). Visual acuity was improved in 2 of 5 patients (Table 3). Ophthalmological assessment of color vision, fundal changes, visual fields and intraocular pressure is presented in Table 4. Five of 9 patients experienced loss or amelioration of diplopia after a 3-6 month treatment. The ocular motility was normalized or improved in 9 of 10 patients. The extraocular muscle enlargement on orbital CT scans decreased in 10 patients (mean score before and after treatment was 6.9 and 3.8 respectively). Minimal and transient side effects were observed during treatment. DISCUSSION: The best parameters of severity of the disease and of response to treatment are those related to assessment of optic nerve function, ocular motility and corneal status [6, 10]. In this series of 14 patients treated with high-dose steroids we found an improvement in visual acuity and color vision and normalization of visual fields, intraocular pressure, visual evoked potentials and fundal changes within a few days of treatment. Clinical activity score (CAS) was significantly and promptly reduced by therapy as most reports revealed [3, 5, 8]. CAS has a high predictive value for the outcome of treatment since it is based on signs of inflammation. The low score level, however, does not preclude a therapeutic success [9]. A mean value of proptosis was significantly reduced by thera

Adult↗

Color space distortions in patients with type 2 diabetes mellitus.

Color vision impairment was examined in patients with type 2 diabetes mellitus (DM2) without retinopathy. We assessed the type and degree of distortions of individual color spaces. DM2 patients (n = 32), and age-matched controls (n = 20) were tested using the Farnsworth D-15 and the Lanthony D-15d tests. In addition, subsets of caps from both tests were employed in a triadic procedure (Bimler & Kirkland, 2004). Matrices of inter-cap subjective dissimilarities were estimated from each subject's "odd-one-out" choices, and processed using non-metric multidimensional scaling. Two-dimensional color spaces, individual and group (DM2 patients; controls), were reconstructed, with the axes interpreted as the R/G and B/Y perceptual opponent systems. Compared to controls, patient results were not significant for the D-15 and D-15d. In contrast, in the triadic procedure the residual distances were significantly different compared to controls: right eye, P = 0.021, and left eye, P = 0.022. Color space configurations for the DM2 patients were compressed along the B/Y and R/G dimensions. The present findings agree with earlier studies demonstrating diffuse losses in early stages of DM2. The proposed method of testing uses color spaces to represent discrimination and provides more differentiated quantitative diagnosis, which may be interpreted as the perceptual color system affected. In addition, it enables the detection of very mild color vision impairment that is not captured by the D-15d test. Along with fundoscopy, individual color spaces may serve for monitoring early functional changes and thereby to support a treatment strategy.

Adult↗

Cone pigment variations in four genera of new world monkeys.

Previous research revealed significant individual variations in opsin genes and cone photopigments in several species of platyrrhine (New World) monkeys and showed that these in turn can yield significant variations in color vision. To extend the understanding of the nature of color vision in New World monkeys, electroretinogram flicker photometry was used to obtain spectral sensitivity measurements from representatives of four platyrrhine genera (Cebus, Leontopithecus, Saguinus, Pithecia). Animals from each genus were found to be polymorphic for middle to long-wavelength (M/L) sensitive cones. The presence of a short-wavelength sensitive photopigment was established as well so these animals conform to the earlier pattern in predicting that all male monkeys are dichromats while, depending on their opsin gene array, individual females can be either dichromatic or trichromatic. Across subjects a total of five different M/L cone pigments were inferred with a subset of three of these present in each species.

Adaptation, Ocular↗

Autosomal dominant cone-rod retinal dystrophy (CORD6) from heterozygous mutation of GUCY2D, which encodes retinal guanylate cyclase.

OBJECTIVE: To describe the clinical features of autosomal dominant cone-rod retinal dystrophy (CRD) in a British family mapping to chromosome 17p12-p13 (CORD6), with a heterozygous mutation (Glu837Asp/ Arg838Ser) of GUCY2D. DESIGN: A prospective, clinical family survey. PATIENTS: Ten affected members of a family with autosomal dominant CRD. METHODS: Full clinical examinations were undertaken. Selected affected family members underwent electrophysiologic evaluation, scotopic static perimetry, dark adaptometry, and color vision assessment. MAIN OUTCOME MEASURES: Clinical appearance and electroretinographic responses. RESULTS: Typical clinical and electroretinographic features of childhood-onset CRD were recorded. In addition, moderate myopia and pendular nystagmus were seen in affected individuals. Color vision assessment in the youngest affected individual showed no color discrimination on a tritan axis, but retention of significant red-green discrimination. Electronegative electroretinogram responses were seen on electrophysiology in the only young family member examined. CONCLUSIONS: The phenotype associated with GUCY2D CRD is clinically distinct from that associated with other dominant CRD loci. Unusual electroretinographic responses may indicate that this mutation of GUCY2D is associated with early defects in photoreceptor synaptic transmission to second-order neurons.

Adolescent↗

Blue-yellow vision deficits in patients with diabetes.

Home blood glucose monitoring has been introduced as a means to achieve good control in patients with diabetes mellitus. Many patients use color-reagent strips and color comparisons to determine blood glucose levels. Intact color vision in the blue-yellow range is necessary for accurately interpreting these strips.Blue-yellow vision deficits occur as a consequence of eye disease and are not genetic or sex-linked. We evaluated blue-yellow vision acuity in 70 diabetic patients and in 19 age-matched control subjects. The patients with diabetes were subdivided according to their degree of retinopathy as follows: no disease (N = 14), nonproliferative diabetic retinopathy (N = 16), proliferative diabetic retinopathy (N = 14) and postlaser-treated (N = 26). None of the control group had deficits. Each group of diabetic patients had a statistically significant increase in color vision deficits compared with the controls. In the laser-treated group, deficits occurred in most patients, were more severe and were significantly increased over all other diabetic subgroups. These deficits may impair visual interpretation of home blood glucose monitoring strips.

Aged↗

[Clinical diagnostic prerequisites for adult vitelliform macular dystrophy].

BACKGROUND: Adult vitelliform macular dystrophy (AVMD) was first described in 1974 (Gass) but is still often misdiagnosed. Large studies using modern morphological and functional diagnostic methods do not exist. PATIENTS AND METHODS: The records of 67 consecutive AVMD patients (1994-2003) were reviewed regarding color vision, perimetry, RPE autofluorescence, fluorescein angiography, EOG, ERG, and mfERG. RESULTS: The mean age was 54.8 years. Symptoms, visual loss, color vision deficits, and visual field defects were highly variable. Autofluorescence was increased centrally in 77% of the eyes. In the ERG, the 30 Hz flicker response was reduced in 71% of the eyes. MfERGs showed a marked central amplitude reduction in 62% of the eyes and a continual normalization of the P1 amplitude towards the periphery. CONCLUSION: The enhanced autofluorescence indicates increased lipofuscin in the vitelliform lesions. The electroretinographic recordings reveal a moderate generalized cone dysfunction with increased severity towards the fovea. Ophthalmoscopy, autofluorescence, and recording of mfERG are prerequisites to diagnose AVMD correctly.

Adult↗

Repeatability indices for the Farnsworth D-15 test.

The repeatability of the D-15 color-vision test is considered to be excellent. However, this conclusion is based on a subject pool which contained a large percentage of color-normals. This type of sampling could bias the repeatability results because color-normals rarely fail the test. Furthermore, color-normals usually do not perform the D-15 in the clinical setting. To establish the repeatability of the D-15 for a relevant clinical population, we examined the D-15 results from two different sessions for 116 subjects who had a congenital red-green color-vision defect. The kappa coefficient for intersession agreement indicated that approximately 84% of the subjects obtained the same pass/fail results at both sessions. The type of defect was repeatable on approximately 80% of the subjects. Although the repeatability of the D-15 for color-defective subjects was good, it was lower than the near-perfect agreement reported previously. The coefficients of repeatability for the crossings show that if a person makes less than five crossings then the test should be administered again in order to ensure that the test result is repeatable.

Adult↗

Red glasses and visual function in retinitis pigmentosa.

UNLABELLED: As a consequence of animal reduction of the light regimes have been tried on patients with retinitis pigmentosa. The trials have been very limited and have not given reason for hope that such reduced light therapy may be beneficial. However, RP patients trying red glasses have reported acute subjective improvement of their visual function. It was the purpose of this study to try to document the reports more objectively. Five visual functions were tested with and without red glasses with the following results: 1. Visual acuity and contrast sensitivity. For one volunteer a small reproducible improvement was found. 2. Color vision. In most cases deterioration was found of already deficient color vision. 3. Visual fields. For volunteers with relatively preserved vision no difference or slight deterioration was found. For the other volunteers slight improvements were found. 4. Intraocular light scatter. No differences were found. 5. Dark adaptation. Improvements were found when the glasses were used as adaptation aid according to the method of Trendelenburg (rod function). For cone function no difference was found upon continuous wearing of red glasses. IN CONCLUSION: use of red glasses does not seem to be of great benefit as a rule. On the other hand, apart from the reduction in color discrimination no serious disadvantages seem to be inherent in their wear by RP patients.

Color↗

[Methods for screening and surveillance of diabetic retinopathy].

PURPOSE: The aim of this study is to investigate the various tests which allow to detect and follow-up diabetic retinopathy (DR). METHODS: Sixteen patients without DR or with background retinopathy underwent, once every six months: a full ophthalmologic investigation; a fluorescein angiography; a color vision test; a central visual field investigation. RESULTS: The impairment of angiography preceeded damage of eye fundus in 27% of cases. Deficiency of color vision and visual field were found in 57% of cases and in 35% respectively. These preceeded the appearance of angiographic DR in 50% of cases and 32% of cases respectively. CONCLUSION: The importance of such tools in the evolution of DR especially in young diabetics is discussed.

Adult↗

A general zone theory of color and brightness vision. II. The space-time field.

The elements of vision are brightness and color varying in time and space, constituting a vector space-time function: the visual sensation field. The sensory-field generated from the light-field variations on the retina is analyzed here in terms of elemental space-time responses (Green's functions). Both chromaticity and intensity variations in either time or space are included in a unified theory, to bridge the existing gap between color theory and analyses of spatial and temporal brightness. Sensory Green's functions are here related to standard color models and to familiar responses for special stimuli, and are shown to be advantageous for nonhomogeneous and/or nonstationary visual conditions. The theory is first applied for intensity space-time variations, to elucidate existing intensity-contrast analyses. Then the general theory including chromatic contrast is illustrated by deriving color vision generalizations of the Bloch and Ricco laws and a general space-time reciprocity law, by analyses of wavelength-pulse and color-flicker experiments, and by derivation of Abney's law of luminance additivity for heterochromoatic flicker and minimally distinct borders.

Color↗

D-15 performance with short wavelength absorbing filters in normals.

Short wavelength absorbing filters (SWAF's) have become very popular in the prescription and commercial sunglass markets. Like other chromatic filters SWAF's have the potential to alter color vision. Performance on the Farnsworth Panel D-15 (D-15) test was measured to determine whether any of 4 popular SWAF's, in the form of sunglasses, produced color vision changes in 22 color normal adults. Using standard illuminant C, observers were tested under the following conditions: wearing no filter, a 1.0 log unit neutral density filter (NDF), or one of the following SWAF's: Corning CPF 550; NolR Amber 40%; Blu Blocker; and Vuarnet 4006. In addition, the Vuarnets were tested outdoors in shaded daylight to determine the effects of increased illumination. The NDF served as the control and had no effect on D-15 performance. Compared to it, only the Blu Blockers and Vuarnets affected D-15 cap arrangements for these SWAF's significantly. Blu Blocker error patterns had no predominant axis, whereas the predominant axis of errors in both Vuarnet conditions was tritan. Results of quantitative analysis performed on three factors confirmed these findings and indicated the Blu Blockers and Vuarnet SWAF's caused moderate and moderate-to-severe levels of color confusion, respectively. Increasing the illumination level improved performance with the Vuarnets, but it remained significantly outside the normal range.

Adult↗

Neuropsychological sequelae of exposure to welding fumes in a group of occupationally exposed men.

This study compares the neuropsychological function, emotional status, visual function, and illness prevalence of 76 former and current chemical industry welders primarily involved in steel welding, and exposed to welding fumes for an average of 24.9 years with that of 42 unexposed, non-welder controls. Health and occupational history questionnaires were administered, as were the neuropsychological tests included in the World Health Organization Neurobehavioral Core Test Battery, Luria Motor Test, and selected tests from the WAIS-III, and WMS-III. Emotional status tests included the BSI, POMS, BAI, and BDI, and vision tests included the Snellen near visual acuity, Lanthony d-15 color vision, Vistech Contrast Sensitivity, and Schirmer strips. While welders and controls performed similarly on tests of verbal skills, verbal retention, and auditory span, welders performed worse than controls on tests of verbal learning, working memory, cognitive flexibility, visuomotor processing speed, and motor efficiency. Welders had poorer color vision and emotional status, and increased prevalence of illnesses and psychiatric symptoms. The increased symptoms in welders were related to decreased scores on tasks measuring verbal learning, visuomotor abilities, visuospatial abilities, and information processing, and motor efficiency. Within the group of welders, the number of hours welding was negatively related to scores on verbal learning, auditory span, working memory, cognitive flexibility, and motor efficiency.

Adult↗

HIV-related ocular microangiopathic syndrome and color contrast sensitivity.

PURPOSE: Color vision deficits in patients with acquired immunodeficiency syndrome (AIDS) or human immunodeficiency virus (HIV) disease were reported, and a retinal pathogenic mechanism was proposed. The purpose of this study was to evaluate the association of color vision deficits with HIV-related retinal microangiopathy. METHODS: A computer graphics system was used to measure protan, deutan, and tritan color contrast sensitivity (CCS) thresholds in 60 HIV-infected patients. Retinal microangiopathy was measured by counting the number of cotton-wool spots, and conjunctival blood-flow sludging was determined. Additional predictors were CD4+ count, age, time on aerosolized pentamidine, time on zidovudine, and Walter Reed staging. The relative influence of each predictor was calculated by stepwise multiple regression analysis (inclusion criterion; incremental P value = < 0.05) using data for the right eyes (RE). The results were validated by using data for the left eyes (LE) and both eyes (BE). RESULTS: The only included predictors in multiple regression analyses for the RE were number of cotton-wool spots (tritan: R = .70; deutan: R = .46; and protan: R = .58; P < .0001 for all axes) and age (tritan: increment of R [Ri] = .05, P = .002; deutan: Ri = .10, P = .004; and protan: Ri = .05, P = .002). The predictors time on zidovudine (Ri = .05, P = .002) and Walter Reed staging (Ri = .03, P = .01) were additionally included in multiple regression analysis for tritan LE. The results for deutan LE were comparable to those for the RE. In the analysis for protan LE, the only included predictor was number of cotton-wool spots. In the analyses for BE, no further predictors were included. The predictors Walter Reed staging and CD4+ count showed a significant association with all three criteria in univariate analysis. Additionally, tritan CCS was significantly associated with conjunctival blood-flow sludging. CONCLUSION: CCS deficits in patients with HIV disease are primarily associated with the number of cotton-wool spots. Results of this study are in accordance with the hypothesis that CCS deficits are in a relevant part caused by neuroretinal damage secondary to HIV-related microangiopathy.

Acquired Immunodeficiency Syndrome↗