Structural Analysis of Glaucoma Brain and its Association With Ocular Parameters.

PRECIS: Glaucoma patients presented a decreased occipital pole surface area in both hemispheres. Moreover, these parameters are independently correlated with functional and structural ocular parameters. PURPOSE: The purpose of this study was to evaluate structural brain abnormalities in glaucoma patients using 3-Tesla magnetic resonance imaging and assess their correlation with associated structural and functional ocular findings. PATIENTS AND METHODS: This cross-sectional prospective study included 30 glaucoma patients and 18 healthy volunteers. All participants underwent standard automated perimetry, spectral-domain optical coherence tomography, and 3.0-Tesla magnetic resonance imaging. RESULTS: There was a significant difference between the surface area of the occipital pole in the left hemisphere of glaucoma patients (mean: 1253.9±149.3 mm) and that of control subjects (mean: 1341.9±129.8 mm), P=0.043. There was also a significant difference between the surface area of the occipital pole in the right hemisphere of glaucoma patients (mean: 1910.5±309.4 mm) and that of control subjects (mean: 2089.1±164.2 mm), P=0.029. There was no significant difference between the lingual, calcarine, superior frontal, and inferior frontal gyri of glaucoma patients and those of the control subjects (P>0.05 for all comparisons). The surface area of the occipital pole in the left hemisphere was significantly correlated with perimetry mean deviation values, visual acuity, age, and retinal nerve fiber layer thickness (P=0.001, <0.001, 0.010, and 0.006, respectively). The surface area of the occipital pole in the right hemisphere was significantly correlated with perimetry mean deviation values, visual field indices, visual acuity, age, and retinal nerve fiber layer thickness (P<0.001, 0.007, <0.001, 0.046, and <0.001, respectively). CONCLUSION: Glaucoma patients presented a decreased occipital pole surface area in both hemispheres that independently correlated with functional and structural ocular parameters.

Contributions of the Melanopsin-Expressing Ganglion Cells, Cones, and Rods to the Pupillary Light Response in Obstructive Sleep Apnea.

Purpose: To investigate the impact of obstructive sleep apnea (OSA) on the contribution of inner and outer retinal photoreceptors to the pupillary light response (PLR). Methods: Ninety-three eyes from 27 patients with OSA and 25 healthy controls were tested. OSA severity was graded according to the apnea-hypopnea index. PLR was measured monocularly with an eye tracker in a Ganzfeld in response to 1-second blue (470 nm) and red (640 nm) flashes at -3, -2, -1, 0, 1, 2, and 2.4 log cd/m2. Peak pupil constriction amplitude, peak latency, and the postillumination pupil response were measured. The Cambridge Colour Test, standard automatic perimetry, spectral domain optical coherence tomography, polysomnography, and the Pittsburgh Sleep Quality Index were used. Results: OSA patients have a significantly decreased peak pupil constriction amplitude for blue stimuli at -3, -2, -1, 1 log cd/m2 and at all red flash luminances (P < 0.050), revealing reduction of outer retina contributions to PLR. OSA patients showed reduced peak latency for blue (-2, 0, 2, 2.4 log cd/m2) and red stimuli (-2, 0 log cd/m2; P < 0.040). No significant difference was found in the melanopsin-mediated PLR. Conclusions: This study is the first to evaluate the inner and outer retinal contributions to PLR in OSA patients. The results showed that the outer retinal photoreceptor contributions to PLR were affected in moderate and severe OSA patients. In contrast, the inner retina contributions to PLR are preserved.

Inner and Outer Retinal Contributions to Pupillary Light Response: Correlation to Functional and Morphologic Parameters in Glaucoma.

PURPOSE: To evaluate in patients with primary open-angle glaucoma (POAG) the contribution of the inner and outer retinal photoreceptors to the pupillary light responses (PLRs) correlated with both functional (color vision and visual field perimetry) and morphologic (optical coherence tomography) parameters. METHODS: In total, 45 patients with POAG and 25 healthy control participants were evaluated. The PLR was measured as pupil diameter with an eye tracker; stimuli were presented in a Ganzfeld. Pupil responses were measured monocularly, to 1 second blue (470 nm) and red (640 nm) flashes with -3, -2, -1, 0, 1, 2, and 2.4 log cd/m luminance levels. Color vision was evaluated with the Cambridge Color Test, visual field was measured by standard automatic perimetry, and retinal nerve fiber layer thickness was evaluated by optical coherence tomography. RESULTS: Patients with moderate and severe POAG have a significantly decreased PLR that depends on the severity of POAG, for both the 470 and 640 nm stimuli, revealing the reduction of the contributions of the rods, cones, and intrinsically photosensitive retinal ganglion cells to PLR. A significant loss of color discrimination along the blue-yellow axis was observed in all stages of POAG. Correlations among standard automatic perimetry, retinal nerve fiber layer thickness, Cambridge Color Test, PLR, and melanopsin parameters were found. CONCLUSIONS: The results provide evidence that in moderate and severe stages of POAG, both the inner and outer retinal contributions to PLR are affected. Also, a worsening in color vision was correlated with reduced PLR responses at high-intensity stimuli. These findings may enhance the clinical management of POAG patients.

Electroretinographical determination of human color vision type.

It has been previously demonstrated that electroretinography (ERG) elicited by heterochromatically modulated stimuli can be used for objective determination of color vision type. Color vision of trichromatic, deuteranopic, and protanopic participants was psychophysically assessed by the Cambridge Color Test and confirmed genetically. ERG responses to red and green lights modulating in counterphase at 12 and 36 Hz were recorded, while the fraction of red modulation was varied. At 36 Hz (and second harmonics at 12 Hz), the responses were minimal at red fractions that differed significantly in protanopes. At 12 Hz (fundamental component), the responses of the trichromats differed significantly compared to those of the dichromats. An improved protocol shows that the three subject groups can be separated with no overlap.

Neurotoxic impact of mercury on the central nervous system evaluated by neuropsychological tests and on the autonomic nervous system evaluated by dynamic pupillometry.

Mercury vapor is highly toxic to the human body. The present study aimed to investigate the occurrence of neuropsychological dysfunction in former workers of fluorescent lamps factories that were exposed to mercury vapor (years after cessation of exposure), diagnosed with chronic mercurialism, and to investigate the effects of such exposure on the Autonomic Nervous System (ANS) using the non-invasive method of dynamic pupillometry. The exposed group and a control group matched by age and educational level were evaluated by the Beck Depression Inventory and with the computerized neuropsychological battery CANTABeclipse - subtests of working memory (Spatial Span), spatial memory (Spatial Recognition Memory), visual memory (Pattern Recognition Memory) and action planning (Stockings of Cambridge). The ANS was assessed by dynamic pupillometry, which provides information on the operation on both the sympathetic and parasympathetic functions. Depression scores were significantly higher among the former workers when compared with the control group. The exposed group also showed significantly worse performance in most of the cognitive functions assessed. In the dynamic pupillometry test, former workers showed significantly lower response than the control group in the sympathetic response parameter (time of 75% of pupillary recovery at 10cd/m2 luminance). Our study found indications that are suggestive of cognitive deficits and losses in sympathetic autonomic activity among patients occupationally exposed to mercury vapor.

Relationship between Daytime Sleepiness and Intrinsically Photosensitive Retinal Ganglion Cells in Glaucomatous Disease.

Patients with glaucoma showed to have higher daytime sleepiness measured by Epworth sleepiness scale. In addition, this symptom was associated with pupillary reflex and polysomnography parameters. These ipRGC functions might be impaired in patients with glaucoma, leading to worse quality of life.

Intrinsically photosensitive retinal ganglion cell activity is associated with decreased sleep quality in patients with glaucoma.

PURPOSE: To use the pupillary light reflex and polysomnography to evaluate the function of intrinsically photosensitive retinal ganglion cells (ipRGCs) and to correlate this function with structural damage in glaucoma. DESIGN: Cross-sectional study. PARTICIPANTS: A study was conducted on both eyes of 45 participants (32 patients with glaucoma and 13 healthy subjects). METHODS: For the pupillary reflex evaluation, patients were tested in the dark using a Ganzfeld system (RETIport; Roland Consult, Brandenburg, Germany); pupil diameter was measured with an eye tracker system. To preferentially stimulate ipRGCs, we used a 1-second 470-nm flash with a luminance of 250 cd/m(2). To stimulate different retinal photoreceptors, we used a 1-second 640-nm flash with a luminance of 250 cd/m(2). All of the subjects underwent polysomnography. Subjects underwent standard automated perimetry and optical coherence tomography (Cirrus HD-OCT; Carl Zeiss Meditec Inc, Dublin, CA). MAIN OUTCOME MEASURES: Correlations between ipRGC activity, as measured by the pupillary light reflex, and polysomnography parameters, and correlations between retinal nerve fiber layer (RNFL) thickness and the pupillary light reflex and polysomnography parameters. RESULTS: The mean patient ages in the healthy and glaucoma groups were 56.8±7.8 years and 61.5±11.6 years, respectively (P = 0.174). Patients with glaucoma had significantly lower average total sleep time, sleep efficiency, and minimum oxyhemoglobin saturation compared with the healthy subjects (P = 0.008, P = 0.002, and P = 0.028, respectively). Patients with glaucoma had significantly higher arousal durations after falling asleep and more periodic limb movements (P = 0.002 and P = 0.045, respectively). There was an inverse correlation between the rapid eye movement latency and the peak of the pupillary response to the blue flash (P = 0.004). The total arousals were inversely correlated with the sustained blue flash response (P = 0.029). The RNFL thickness was associated with the peak and sustained responses to the blue flash (P < 0.001 for both comparisons); however, RNFL thickness was only associated with the mean oxygen desaturation index among the polysomnography parameters (P = 0.023). CONCLUSIONS: This study demonstrated that decreased ipRGC function caused by glaucoma affected pupillary response and sleep quality.

The role of early stages of cortical visual processing in size and distance judgment: a transcranial direct current stimulation study.

Recent research suggests that V1 plays an active role in the judgment of size and distance. Nevertheless, no research has been performed using direct brain stimulation to address this issue. We used transcranial direct-current stimulation (tDCS) to directly modulate the early stages of cortical visual processing while measuring size and distance perception with a psychophysical scaling method of magnitude estimation in a repeated-measures design. The subjects randomly received anodal, cathodal, and sham tDCS in separate sessions starting with size or distance judgment tasks. Power functions were fit to the size judgment data, whereas logarithmic functions were fit to distance judgment data. Slopes and R(2) were compared with separate repeated-measures analyses of variance with two factors: task (size vs. distance) and tDCS (anodal vs. cathodal vs. sham). Anodal tDCS significantly decreased slopes, apparently interfering with size perception. No effects were found for distance perception. Consistent with previous studies, the results of the size task appeared to reflect a prothetic continuum, whereas the results of the distance task seemed to reflect a metathetic continuum. The differential effects of tDCS on these tasks may support the hypothesis that different physiological mechanisms underlie judgments on these two continua. The results further suggest the complex involvement of the early visual cortex in size judgment tasks that go beyond the simple representation of low-level stimulus properties. This supports predictive coding models and experimental findings that suggest that higher-order visual areas may inhibit incoming information from the early visual cortex through feedback connections when complex tasks are performed.

Transcranial direct current stimulation can selectively affect different processing channels in human visual cortex.

Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation technique that can modulate cortical activity. Nonetheless, information regarding its functional specificity and the extent by which visual performance can be modulated is still lacking. Here, we used vision as model to address if it differentially affects different cell groups in the stimulated area. We applied tDCS to the occiput and performed a series of visual tests in a sham-controlled repeated-measures design. Achromatic contrast sensitivity was assessed psychophysically during tDCS, with tasks designed to target specific spatial frequency (SF) channels, inferred ON, OFF channels and inferred magnocellular and parvocellular pathways of the visual system. Sweep visual evoked potential (sVEP) for contrast sensitivity and Vernier acuity was recorded before and after tDCS. Anodal tDCS significantly increased thresholds for luminance decrements (OFF) only for the inferred magnocellular thresholds. Although tDCS had no significant effects on Vernier or contrast sVEP thresholds, it modulated suprathreshold amplitudes for both tasks. Cathodal tDCS increased sVEP amplitudes at a low SF, decreased it at a medium, and had no effect at a high SF. Cathodal tDCS increased sVEP phase lags for low and decreased it for high SF (maximum change corresponding to change in apparent latency >6 ms). Cathodal and anodal stimulation decreased amplitudes of sVEP Vernier responses. Exclusive tDCS effects on magnocellular thresholds agree with reports of pathway-specific tDCS effects. The dependence of tDCS effects on SF and contrast levels further suggests that tDCS differentially affects different cell groups in the visual cortex.

Variability and systematic differences in normal, protan, and deutan color naming.

The congenital color vision deficient (CVD) generally demonstrates difficulties in color naming tasks. In our study we investigated color naming properties and uncertainties of a relatively large group of red-green CVDs using quasi monochromatic stimuli and seven basic color terms. The results show a large variability in color naming for the CVD when contrasted to normal color vision and similar alterations when comparing protans to deutans. Statistically significant differences were found in specific wavelength ranges between the tested groups. In general, protans and deutans have shown better color naming ability than expected, which suggests the use of non-chromatic visual cues.

A positive association between intrinsically photosensitive retinal ganglion cells and retinal nerve fiber layer thinning in glaucoma.

PURPOSE: To assess the integrity of intrinsically photosensitive retinal ganglion cells (ipRGCs) using the pupillary light reflex in glaucoma patients. METHODS: A cross-sectional study was conducted, including 76 eyes from 38 patients with primary open-angle glaucoma and 36 eyes from 18 control subjects. The patients were tested in the dark with light stimuli using the Ganzfeld system, and the pupil diameter was measured with the assistance of an eye tracker consisting of two infrared cameras fit to an eyeglass frame. To preferentially stimulate ipRGCs, we used a 1-second 470-nm flash with a luminance of 250 cd/m(2). To stimulate different retinal photoreceptors (cones and rods), we used a 1-second 630-nm flash with a luminance of 250 cd/m(2). Standard automated perimetry (SAP), matrix frequency-doubling technology (FDT), and high-definition optical coherence tomography (Cirrus HD-OCT) were also performed. The correlation between the ipRGC-mediated sustained response following the pupillary light reflex and the structural and functional changes in glaucoma patients was analyzed using generalized estimating equation. RESULTS: An association was observed between the average retinal nerve fiber layer (RNFL) thickness, as measured by Cirrus HD-OCT, and the sustained pupillary response to the blue flash (P = 0.024). The severity of glaucoma, based on the mean deviation of SAP (Hodapp-Anderson-Parrish system), was also associated with the sustained response to the blue flash (P = 0.006). CONCLUSIONS: This study showed a correlation between the mean RNFL thickness and the pupillary light response. A decrease in the number of ipRGCs is potentially related to the reduced RNFL thickness.

Cross-cultural variation of memory colors of familiar objects.

The effect of cross-regional or cross-cultural differences on color appearance ratings and memory colors of familiar objects was investigated in seven different countries/regions - Belgium, Hungary, Brazil, Colombia, Taiwan, China and Iran. In each region the familiar objects were presented on a calibrated monitor in over 100 different colors to a test panel of observers that were asked to rate the similarity of the presented object color with respect to what they thought the object looks like in reality (memory color). For each object and region the mean observer ratings were modeled by a bivariate Gaussian function. A statistical analysis showed significant (p < 0.001) differences between the region average observers and the global average observer obtained by pooling the data from all regions. However, the effect size of geographical region or culture was found to be small. In fact, the differences between the region average observers and the global average observer were found to of the same magnitude or smaller than the typical within region inter-observer variability. Thus, although statistical differences in color appearance ratings and memory between regions were found, regional impact is not likely to be of practical importance.

The pupil light reflex in Leber's hereditary optic neuropathy: evidence for preservation of melanopsin-expressing retinal ganglion cells.

PURPOSE: To investigate the pupillary light reflex (PLR) of patients with severe loss of vision due to Leber's Hereditary Optic Neuropathy (LHON) in the context of a proposed preservation of melanopsin-expressing retinal ganglion cells (mRGCs). METHODS: Ten LHON patients (7 males; 51.6 ± 14.1 years), with visual acuities ranging from 20/400 to hand motion perception and severe visual field losses, were tested and compared with 16 healthy subjects (7 males; 42.15 ± 15.4 years) tested as controls. PLR was measured with an eye tracker and the stimuli were controlled with a Ganzfeld system. Pupil responses were measured monocularly, to 1 second of blue (470 nm) and red (640 nm) flashes with 1, 10, 100, and 250 cd/m² luminances. The normalized amplitude of peak of the transient PLR and the amplitude of the sustained PLR at 6 seconds after the flash offset were measured. In addition, optical coherence topography (OCT) scans of the peripapillary retinal nerve fiber layer were obtained. RESULTS: The patient's peak PLR responses were on average 15% smaller than controls (P < 0.05), but 5 out of 10 patients had amplitudes within the range of controls. The patients' sustained PLRs were comparable with controls at lower flash intensities, but on average, 27% smaller to the 250 cd/m² blue light, although there was considerable overlap with the PLR amplitudes of control. All patients had severe visual field losses and the retinal nerve fiber layer thickness was reduced to a minimum around the optic disc in 8 of the 10 patients. CONCLUSIONS: The PLR is maintained overall in LHON patients despite the severity of optic atrophy. These results are consistent with previous evidence of selective preservation of mRGCs.

Transcranial direct current stimulation modulates human color discrimination in a pathway-specific manner.

Previous research showed that transcranial direct current stimulation (tDCS) can modulate visual cortex excitability. However, there is no experiment on the effects of tDCS on color perception to date. The present study aimed to investigate the effects of tDCS on color discrimination tasks. Fifteen healthy subjects (mean age of 25.6 ± 4.4 years) were tested with Cambridge Color Test 2.0 (Trivector and ellipses protocols) and a Forced-choice Spatial Color Contrast Sensitivity task (vertical red-green sinusoidal grating) while receiving tDCS. Anodal, cathodal, and sham tDCS were delivered at Oz for 22 min using two square electrodes (25 cm(2) with a current of 1.5 mA) in sessions separated by 7 days. Anodal tDCS significantly increased tritan sensitivity (p < 0.01) and had no significant effect on protan, deutan, or red-green grating discrimination. The effects on the tritan discrimination returned to baseline after 15 min (p < 0.01). Cathodal tDCS reduced the sensitivity in the deutan axis and increased sensitivity in the tritan axis (p < 0.05). The lack of anodal tDCS effects in the protan, deutan, and red-green grating sensitivities could be explained by a "ceiling effect" since adults in this age range tend to have optimal color discrimination performance for these hues. The differential effects of cathodal tDCS on tritan and deutan sensitivities and the absence of the proposed ceiling effects for the tritan axes might be explained by Parvocellular (P) and Koniocellular (K) systems with regard to their functional, physiological, and anatomical differences. The results also support the existence of a systematic segregation of P and K color-coding cells in V1. Future research and possible clinical implications are discussed.