Heterochromatic Flicker Electroretinograms Reflecting Luminance and Cone Opponent Activity in Glaucoma Patients

PURPOSE. To measure heterochromatic flicker electroretinograms (ERGs) at high (36 Hz) and intermediate (12 Hz) temporal frequencies to evaluate luminance and cone opponent responses, respectively, in glaucoma eyes with (perimetric) and without (preperimetric) visual field defects. METHODS. Flicker ERGs were recorded from one randomly chosen dilated eye of 32 patients (mean age, 61 +/- 11 years; 15 men, 17 women) from the Erlangen Glaucoma Registry and from 24 healthy volunteers (mean age, 43 +/- 11 years; 14 men, 10 women). Red and green light-emitting diodes in a Ganzfeld stimulator were sine wave-modulated in counterphase. The responses were measured at 36 Hz, the frequency at which ERGs reflect activity of the luminance pathway, and at 12 Hz, the frequency at which ERGs reflect chromatic activity. RESULTS. Response amplitudes were similar in glaucoma patients and controls. Phase differences were observed in patients with visual field defects (perimetric) compared with the control group at 36 and 12 Hz in the first harmonic and second harmonic responses. Patients without visual field defects (preperimetric) showed phase differences for the second harmonic component at 36 Hz. No age effect on response amplitudes and phases was found in any of the subject groups (controls and patients). CONCLUSIONS. The responses displayed phase differences but not amplitude differences in perimetric glaucoma patients at both 36 and 12 Hz, suggesting that both magnocellular and parvocellular pathways are affected. Preperimetric glaucoma patients also showed phase differences. The response phase may be sensitive to early dysfunction of the inner retina. (ClinicalTrials.gov number, NCT00494923.) (Invest Ophthalmol Vis Sci. 2011;52:6757-6765) DOI:10.1167/iovs.11-7538

Color vision impairment in type 2 diabetes assessed by the D-15d test and the Cambridge Colour Test

Color vision impairment emerges at early stages of diabetes mellitus type 2 (DM2) and may precede diabetic retinopathy or the appearance of vascular alterations in the retina. The aim of the present study was to compare the evaluation of the color vision with two different tests - the Lanthony desaturated D-15d test (a traditional color arrangement test), and the Cambridge Colour Test (CCT) (a computerized color discrimination test) - in patients diagnosed with DM2 without clinical signs of diabetic retinopathy (DR), and in sex- and age-matched control groups. Both color tests revealed statistically significant differences between the controls and the worst eyes of the DM2 patients. In addition, the degree of color vision impairment diagnosed by both tests correlated with the disease duration. The D-15d outcomes indicated solely tritan losses. In comparison, CCT outcomes revealed diffuse losses in color discrimination: 13.3% for best eyes and 29% for worst eyes. In addition, elevation of tritan thresholds in the DM2 patients, as detected by the Trivector subtest of the CCT, was found to correlate with the level of glycated hemoglobin. Outcomes of both tests confirm that subclinical losses of color vision are present in DM2 patients at an early stage of the disease, prior to signs of retinopathy. Considering the advantages of the CCT test compared to the D-15d test, further studies should attempt to verify and/or improve the efficiency of the CCT test.

Color-space distortions following long-term occupational exposure to mercury vapor

Color vision was examined in subjects with long-term occupational exposure to mercury (Hg) vapor. The color vision impairment was assessed by employing a quantitative measure of distortion of individual and group perceptual color spaces. Hg subjects (n = 18; 42.1 +/- 6.5 years old; exposure time = 10.4 +/- 5.0 years; time away from the exposure source = 6.8 +/- 4.6 years) and controls (n = 18; 46.1 +/- 8.4 years old) were examined using two arrangement tests, D-15 and D-15d, in the traditional way, and also in a triadic procedure. From each subject`s `odd-one-out` choices, matrices of inter-cap subjective dissimilarities were derived and processed by non-metric multidimensional scaling (MDS). D-15d results differed significantly between the Hg-group and the control group (p < 0.05), with the impairment predominantly along the tritan axis. 2D perceptual color spaces, individual and group, were reconstructed, with the dimensions interpreted as the red-green (RG) and the blue-yellow (BY) systems. When color configurations from the Hg-group were compared to those of the controls, they presented more fluctuations along both chromatic dimensions, indicating a statistically significant difference along the BY axis. In conclusion, the present findings confirm that color vision impairments persist in subjects that have received long-term occupational exposure to Hg-vapor although, at the time of testing, they were presenting mean urinary concentration within the normal range for non-exposed individuals. Considering the advantages of the triadic procedure in clinical evaluation of acquired color vision deficiencies, further studies should attempt to verify and/or improve its efficacy.

Absence of ocular interaction in flicker ERG responses reflecting cone opponent and luminance signals

The aim of the study was to investigate whether there is an ocular interaction in the flicker ERG responses reflecting luminance and cone opponency in normal human subjects. Flicker ERGs were recorded from one dilated eye of 10 healthy volunteers. Each subject was tested twice: once with and once without occluding the opposite eye. Red and green LEDs were modulated in counterphase in a Ganzfeld stimulator. ERG responses were recorded for different ratios of the modulation in the red and green LEDs and at 12 and 36 Hz. The amplitudes and phases of the fundamental components were compared between the conditions with and without occlusion. The 12-Hz flicker ERGs reflected activity of the cone opponent channel, whereas the 36-Hz data reflected luminance activity. There were no significant differences between the conditions with and without occluding the opposite eye for any of the stimulus protocols. Ocular interaction is absent in flicker ERGs reflecting cone opponent and luminance activity.

Preliminary Findings on the Effects of Occupational Exposure to Mercury Vapor Below Safety Levels on Visual and Neuropsychological Functions

Objective: To evaluate whether there are visual and neurophysical decrements in workers with low exposure to Hg vapor. Methods: Visual fields, contrast sensitivity, color vision, and neuropsychological functions were measured in 10 workers (32.5 +/- 8.5 years) chronically exposed to Hg vapor (4.3 +/- 2.8 years; urinary Hg concentration 22.3 +/- 9.3 mu g/g creatinine). Results: For the worst eyes, we found altered visual field thresholds, lower contrast sensitivity, and color discrimination compared with controls (P < 0.05). There were no significant differences between Hg-exposed subjects and controls on. neuropsychological tests. Nevertheless, duration of exposure was statistically correlated to verbal memory and depression scores. Conclusions: Chronic exposure to Hg vapor at currently accepted safety levels was found to be associated with visual losses but not with neuropsychological dysfunctions in the sample of workers studied. (J Occup Environ Med. 2009,51:1403-1412)

Irreversible color vision losses in patients with chronic mercury vapor intoxication

This longitudinal study addresses the reversibility of color vision losses in subjects who had been occupationally exposed to mercury vapor. Color discrimination was assessed in 20 Hg-exposed patients (mean age = 42.4 +/- 6.5 years; 6 females and 14 males) with exposure to Hg vapor during 10.5 +/- 5.3 years and away from the work place (relative to 2002) for 6.8 +/- 4.2 years. During the Hg exposure or up to one year after ceasing it, mean urinary Hg concentration was 47 +/- 35.4 mu g/g creatinine. There was no information on Hg urinary concentration at the time of the first tests, in 2002 (Ventura et al., 2005), but at the time of the follow-up tests, in 2005, this value was 1.4 +/- 1.4 mu g/g creatinine for patients compared with 0.5 +/- 0.5 mu g/g creatinine for controls (different group from the one in Ventura et al. (2005)). Color vision was monocularly assessed using the Cambridge Colour Test (CCT). Hg-exposed patients had significantly worse color discrimination (p < 0.02) than controls, as evaluated by the size of MacAdam`s color discrimination ellipses and color discrimination thresholds along protan, deutan, and tritan confusion axes. There were no significant differences between the results of the study in Ventura et al. (2005) and in the present follow-up measurements, in 2005, except for worsening of the tritan thresholds in the best eye in 2005. Both chromatic systems, blue-yellow and red-green, were affected in the first evaluation (Ventura et al., 2005) and remained impaired in the follow-up testing, in 2005. These findings indicate that following a long-term occupational exposure to Hg vapor, even several years away from the source of intoxication, color vision impairment remains irreversible.

Visual field losses in workers exposed to mercury vapor

Visual field losses associated with mercury (Hg) exposure have only been assessed in patients exposed to methylmercury. Here we evaluate the automated visual field in 35 ex-workers (30 males; 44.20+/-5.92 years) occupationaly exposed to mercury vapor and 34 controls (21 males; 43.29+/-8.33 years). Visual fields were analyzed with the Humphrey Field Analyzer II (model 750i) using two tests: the standard automated perimetry (SAP, white-on-white) and the short wavelength automated perimetry (SWAP, blue-on-yellow) at 76 locations within a 27 degrees central visual field. Results were analyzed as the mean of the sensitivities measured at the fovea, and at five successive concentric rings, of increasing eccentricity, within the central field. Compared to controls, visual field sensitivities of the experimental group measured using SAP were lower for the fovea as well as for all five eccentricity rings (p<0.05). Sensitivities were significantly lower in the SWAP test (p<0.05) for four of the five extra-foveal eccentricity rings; they were not significant for the fovea (p = 0.584) or for the 15 degrees eccentricity ring (p = 0.965). These results suggest a widespread reduction of sensitivity in both visual field tests. Previous reports in the literature describe moderate to severe concentric constriction of the visual field in subjects with methylmercury intoxication measured manually with the Goldman perimeter. The present results amplify concerns regarding potential medical risks of exposure to environmental mercury sources by demonstrating significant and widespread reductions of visual sensitivity using the more reliable automated perimetry. (C) 2007 Elsevier Inc. All rights reserved.

Contrast Sensitivity Mediated by Inferred Magno- and Parvocellular Pathways in Type 2 Diabetics with and without Nonproliferative Retinopathy

PURPOSE. To evaluate achromatic contrast sensitivity (CS) with magnocellular-(M) and parvocellular-(P) probing stimuli in type 2 diabetics, with (DR) or without (NDR) nonproliferative retinopathy. METHODS. Inferred M-and P-dominated responses were assessed with a modified version of the steady-/pulsed-pedestal paradigm (SP/PP) applied in 26 NDR (11 male; mean age, 55 +/- 9 years; disease duration, 5 +/- 4 years); 19 DR (6 male; mean age, 58 +/- 7 years; disease duration = 9 +/- 6 years); and 18 controls (CTRL; 12 male; mean age, 55 +/- 10 years). Thresholds were measured with pedestals at 7, 12, and 19 cd/m(2), and increment durations of 17 and 133 ms. The thresholds from the two stimulus durations were used to estimate critical durations (Tc) for each data set. RESULTS. Both DR and NDR patients had significant reduction in CS in both SP and PP paradigms in relation to CTRL (Kruskal-Wallis, P < 0.01). Patients` critical duration estimates for either paradigm were not significantly different from CTRL. CONCLUSIONS. The significant reduction of CS in both paradigms is consistent with losses of CS in both M and P pathways. The CS losses were not accompanied by losses in temporal processing speed in either diabetic group. Significant CS loss in the group without retinopathy reinforces the notion that neural changes associated with the cellular and functional visual loss may play an important role in the etiology of diabetic visual impairment. In addition, the results show that the SP/PP paradigm provides an additional tool for detection and characterization of the early functional damage due to diabetes. (Invest Ophthalmol Vis Sci. 2011; 52:1151-1155) DOI:10.1167/iovs.09-3705

Long-Term Occupational Exposure to Organic Solvents Affects Color Vision, Contrast Sensitivity and Visual Fields

The purpose of this study was to evaluate the visual outcome of chronic occupational exposure to a mixture of organic solvents by measuring color discrimination, achromatic contrast sensitivity and visual fields in a group of gas station workers. We tested 25 workers (20 males) and 25 controls with no history of chronic exposure to solvents (10 males). All participants had normal ophthalmologic exams. Subjects had worked in gas stations on an average of 9.6 +/- 6.2 years. Color vision was evaluated with the Lanthony D15d and Cambridge Colour Test (CCT). Visual field assessment consisted of white-on-white 24-2 automatic perimetry (Humphrey II-750i). Contrast sensitivity was measured for sinusoidal gratings of 0.2, 0.5, 1.0, 2.0, 5.0, 10.0 and 20.0 cycles per degree (cpd). Results from both groups were compared using the Mann-Whitney U test. The number of errors in the D15d was higher for workers relative to controls (p<0.01). Their CCT color discrimination thresholds were elevated compared to the control group along the protan, deutan and tritan confusion axes (p<0.01), and their ellipse area and ellipticity were higher (p<0.01). Genetic analysis of subjects with very elevated color discrimination thresholds excluded congenital causes for the visual losses. Automated perimetry thresholds showed elevation in the 9 degrees, 15 degrees and 21 degrees of eccentricity (p<0.01) and in MD and PSD indexes (p<0.01). Contrast sensitivity losses were found for all spatial frequencies measured (p<0.01) except for 0.5 cpd. Significant correlation was found between previous working years and deutan axis thresholds (rho = 0.59; p<0.05), indexes of the Lanthony D15d (rho = 0.52; p<0.05), perimetry results in the fovea (rho = -0.51; p<0.05) and at 3, 9 and 15 degrees of eccentricity (rho = -0.46; p<0.05). Extensive and diffuse visual changes were found, suggesting that specific occupational limits should be created.

Sequence and Copy Number Analyses of HEXB Gene in Patients Affected by Sandhoff Disease: Functional Characterization of 9 Novel Sequence Variants

Sandhoff disease (SD) is a lysosomal disorder caused by mutations in the HEXB gene. To date, 43 mutations of HEXB have been described, including 3 large deletions. Here, we have characterized 14 unrelated SD patients and developed a Multiplex Ligation-dependent Probe Amplification (MLPA) assay to investigate the presence of large HEXB deletions. Overall, we identified 16 alleles, 9 of which were novel, including 4 sequence variation leading to aminoacid changes [c.626C>T (p.T209I), c.634C>A (p.H212N), c.926G>T (p.C309F), c.1451G>A (p.G484E)] 3 intronic mutations (c.1082+5G>A, c.1242+1G>A, c.1169+5G>A), 1 nonsense mutation c.146C>A (p.S49X) and 1 small in-frame deletion c.1260_1265delAGTTGA (p.V421_E422del). Using the new MLPA assay, 2 previously described deletions were identified. In vitro expression studies showed that proteins bearing aminoacid changes p.T209I and p.G484E presented a very low or absent activity, while proteins bearing the p.H212N and p.C309F changes retained a significant residual activity. The detrimental effect of the 3 novel intronic mutations on the HEXB mRNA processing was demonstrated using a minigene assay. Unprecedentedly, minigene studies revealed the presence of a novel alternative spliced HEXB mRNA variant also present in normal cells. In conclusion, we provided new insights into the molecular basis of SD and validated an MLPA assay for detecting large HEXB deletions.

Influence of low-level laser associated with osteogenic proteins recombinant human BMP-2 and Hevea brasiliensis on bone repair in Wistar rats

This study analyzed the newly formed bone tissue after application of recombinant human BMP-2 (rhBMP-2) and P-1 (extracted from Hevea brasiliensis) proteins, 2 weeks after the creation of a critical bone defect in male Wistar rats treated or not with a low-intensity laser (GaAlAs 780 nm, 60 mW of power, and energy density dose of 30 J/cm2). The animals were divided into two major groups: (1) bone defect plus low-intensity laser treatment and (2) bone defect without laser irradiation. The following subgroups were also analyzed: (a) 5 mu g of pure rhBMP-2; (b) 5 mu g of pure P-1 fraction; (c) 5 mu g of rhBMP-2/monoolein gel; (d) 5 mu g of P-1 fraction/monoolein gel; (e) pure monoolein gel. Comparisons of the groups receiving laser treatment with those that did not receive laser irradiation show differences in the areas of new bone tissue. The group treated with 5 mu g of rhBMP-2 and laser irradiation was not significantly different (P >0.05) than the nonirradiated group that received the same treatment. The irradiated, rhBMP-2/monoolein gel treatment group showed a lower area of bone formation than the nonirradiated, rhBMP-2/gel monoolein treatment group (P < 0.001). The area of new bone tissue in the other nonirradiated and irradiated groups was not significantly different (P > 0.05). Furthermore, the group that received the 5 mu g of rhBMP-2 application showed the greatest bone formation. We conclude that the laser treatment did not interfere with the area of new bone tissue growth and that the greatest stimulus for bone formation involved application of the rhBMP-2 protein. Microsc. Res. Tech. 2011. (c) 2011 Wiley Periodicals, Inc.

Prevalência e motivos de remoção não eletiva do cateter central de inserção periférica em neonatos

Estudo transversal, realizado com 67 recém-nascidos internados em uma Unidade de Terapia Intensiva Neonatal de um hospital privado de São Paulo, entre julho e dezembro de 2010, submetidos a 84 inserções de Cateteres Centrais de Inserção Periférica (CCIP). Os objetivos foram descrever a prevalência de remoção não eletiva do cateter e seus motivos. Os dados foram coletados de prontuários médicos e do formulário de registro de informações sobre o cateter. A média de idade gestacional corrigida dos neonatos foi 32,8 semanas, peso 1.671,6 g e idade pós-natal 9,4 dias. A remoção não eletiva ocorreu em 33 (39,3%) cateteres, 13,1% por obstrução, 9,5% ruptura, 7,1% edema do membro, 6% suspeita de infecção, 1,2% tração acidental, 1,2% má perfusão e 1,2% extravasamento. A prevalência e os motivos de remoção não eletiva indicaram a necessidade de estratégias para a prevenção de complicações evitáveis relacionadas ao CCIP.