Pupillary Light Reflex Reveals Melanopsin System Alteration in the Background of Myopia-26, the Female Limited Form of Early-Onset High Myopia.

Purpose: The purpose of this study was to evaluate pupillary light reflex (PLR) to chromatic flashes in patients with early-onset high-myopia (eoHM) without (myopic controls = M-CTRL) and with (female-limited myopia-26 = MYP-26) genetic mutations in the ARR3 gene encoding the cone arrestin. Methods: Participants were 26 female subjects divided into 3 groups: emmetropic controls (E-CTRL, N = 12, mean age = 28.6 ± 7.8 years) and 2 myopic (M-CTRL, N = 7, mean age = 25.7 ± 11.5 years and MYP-26, N = 7, mean age = 28.3 ± 15.4 years) groups. In addition, one hemizygous carrier and one control male subject were examined. Direct PLRs were recorded after 10-minute dark adaptation. Stimuli were 1-second red (peak wavelength = 621 nm) and blue (peak wavelength = 470 nm) flashes at photopic luminance of 250 cd/m². A 2-minute interval between the flashes was introduced. Baseline pupil diameter (BPD), peak pupil constriction (PPC), and postillumination pupillary response (PIPR) were extracted from the PLR. Group comparisons were performed with ANOVAs. Results: Dark-adapted BPD was comparable among the groups, whereas PPC to the red light was slightly reduced in patients with myopia (P = 0.02). PIPR at 6 seconds elicited by the blue flash was significantly weaker (P < 0.01) in female patients with MYP-26, whereas it was normal in the M-CTRL group and the asymptomatic male carrier. Conclusions: L/M-cone abnormalities due to ARR3 gene mutation is currently claimed to underlie the pathological eye growth in MYP-26. Our results suggest that malfunction of the melanopsin system of intrinsically photosensitive retinal ganglion cells (ipRGCs) is specific to patients with symptomatic MYP-26, and may therefore play an additional role in the pathological eye growth of MYP-26.

Electroretinographic oscillatory potentials in Leber hereditary optic neuropathy.

PURPOSE: Leber hereditary optic neuropathy (LHON) affects retinal ganglion cells causing severe vision loss. Pattern electroretinogram and photopic negative response (PhNR) of the light-adapted (LA) full-field electroretinogram (ERG) are typically affected in LHON. In the present study, we evaluated dark-adapted (DA) and LA oscillatory potentials (OPs) of the flash ERG in genetically characterized LHON patients to dissociate slow from fast components of the response. METHODS: Seven adult patients (mean age = 28.4 ± 5.6) in whom genetic diagnosis confirmed LHON with mtDNA or nuclear DNAJC30 (arLHON) pathogenic variants were compared to 12 healthy volunteers (mean age = 35.0 ± 12.1). Full-field ERGs were recorded from both eyes. Offline digital filters at 50, 75 and 100 Hz low cutoff frequencies were applied to isolate high-frequency components from the original ERG signals. RESULTS: ERG a-waves and b-waves were comparable between LHON patients and controls, while PhNR was significantly reduced (p = 0.009) in LHON patients compared to controls, as expected. OPs derived from DA signals (75 Hz low cutoff frequency) showed reduced peak amplitude for OP2 (p = 0.019). LA OP differences between LHON and controls became significant (OP2: p = 0.047, OP3: p = 0.039 and OP4: p = 0.013) when the 100 Hz low-cutoff frequency filter was applied. CONCLUSIONS: Reduced OPs in LHON patients may represent disturbed neuronal interactions in the inner retina with preserved photoreceptoral (a-wave) to bipolar cell (b-wave) activation. Reduced DA OP2 and high-cutoff LA OP alterations may be further explored as functional measures to characterize LHON status and progression.

Retinal Function in Patients with Adalimumab Treatment: Long-term Follow-up with Microperimetry.

Purpose: To examine the effects of a biological treatment (adalimumab) on visual function in patients with ankylosing spondylitis and in uveitic patients without macular edema during one-year treatment with adalimumab.Methods: Sixteen eyes of eight consecutive Caucasian patients treated with adalimumab were followed up using microperimetry (MAIA; CenterVue, Padova, Italy). Five patients had ankylosing spondylitis without uveitis, three patients had panuveitis without macular edema. Macular sensitivity and macular integrity were recorded.Results: During six-month follow-up, the average threshold did not change significantly (p = .649). Macular integrity was stable (p = .225). The macular sensitivity point analysis showed no significant effects (examination F(3,56) = 0.494 and p = .688; point*examination F(108,2016) = 0.688 and p = .994) during the follow-up.Conclusions: During one-year follow-up, adalimumab did not affect macular function, unlike the well-established maculopathy induced by hydroxychloroquine. Microperimetry may be considered when following-up macular function in patients undertaking adalimumab.

Preliminary Findings on the Optimization of Visual Performance in Patients with Age-Related Macular Degeneration Using Biofeedback Training.

Biofeedback training has been used to improve fixation stability in subjects with central vision loss, but the psychophysiological mechanisms underlying the functional improvements resulted was not reported. The aim of this study was to investigate the effects of microperimetric biofeedback training on different visual functions and self-reported quality of vision in subjects with age-related macular degeneration. This case-control study included six subjects (72.0 ± 6.1 years of age) diagnosed with age-related macular degeneration (wet or dry) with low vision (best corrected visual acuity ranging from 0.5 to 0.1 in the study eye) and five healthy volunteers (64.2 ± 3.7 years of age). Ophthalmological and functional examinations were obtained from all subjects twice with an approximately 3-month interval. Subjects with central vision loss performed 12 sessions (10 min each) of biofeedback training between the two examinations. Functional evaluation included: microperimetry, spatial luminance contrast sensitivities, color vision thresholds, visual acuity, and reading speed. Visual performance during daily activities was also assessed using a standardized questionnaire. The ratio (2nd/1st examination) of the spatial luminance contrast sensitivity at lower spatial frequencies were much higher for the training subjects compared with the controls. In addition, self-reported quality of vision improved after the training. The significant improvement of the visual function such as spatial luminance contrast sensitivity may explain the better self-reported quality of vision. Possible structural and physiological mechanisms underlying this neuromodulation are discussed.

Photoreceptor-specific light adaptation of critical flicker frequency in trichromat and dichromat observers.

The silent substitution paradigm offers possibilities to investigate and compare the temporal properties of mechanisms driven by single photoreceptor types, including the critical flicker frequency (CFF), in which the state of adaptation can be kept as invariant. We have (1) measured CFFs using triple silent substitutions to isolate L-, M-, and S-cone as well as rod-driven pathways under identical mean luminances and chromaticities; (2) repeated the CFF measurements at different mean luminances in order to validate the Ferry-Porter law (stating that the relationship between CFF and the log retinal illuminance-log I-is linear); and (3) compared these CFF versus log I functions for L-, M-, S-cone-, and rod-isolating stimuli for five trichromats and four X-linked dichromats (two protanopes, two deuteranopes). We show that the effects of luminance on the CFFs with silent substitution are comparable to those measured previously with chromatic stimuli. We found that M-cone-driven CFFs are smaller in trichromats than in protanopes. Furthermore, the slopes of the M-cone-driven CFF versus log I functions are smaller in trichromats. Possibly, the lacking L-cones are replaced by M-cones in these two protanopes and the CFF depends on cone density. Furthermore, we found that in trichromats, the slopes of the CFF-log I functions are smaller for M-cone- than for L-cone-isolating stimuli. This contradicts the current interpretation of the CFF-log I functions for chromatic stimuli, which states that CFF is mediated by the most strongly modulated photoreceptor type. Thus, the larger slopes that were previously found with medium-wavelength chromatic stimuli compared with long-wavelength chromatic stimuli seem to be the result of an addition of signals from different photoreceptors and do not necessarily result from M-cones being inherently faster.

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.

Color Vision Losses in Autism Spectrum Disorders.

Autism spectrum disorders (ASDs) are neurodevelopmental conditions characterized by impairments in social/communication abilities and restricted behaviors. The present study aims to examine color vision discrimination in ASD children and adolescents without intellectual disability. The participants were also subdivided in order to compare color vision thresholds of autistic participants and those who achieved diagnostic criteria for Asperger Syndrome (AS). Nine subjects with autism, 11 participants with AS and 36 typically developing children and adolescents participated in the study. Color vision was assessed by the Cambridge Color Test (CCT). The Trivector protocol was administered to determine color discrimination thresholds along the protan, deutan, and tritan color confusion lines. Data from ASD participants were compared to tolerance limits for 90% of the population with 90% probability obtained from controls thresholds. Of the 20 ASD individuals examined, 6 (30%) showed color vision losses. Elevated color discrimination thresholds were found in 3/9 participants with autism and in 3/11 AS participants. Diffuse and tritan deficits were found. Mechanisms for chromatic losses may be either at the retinal level and/or reflect reduced cortical integration.

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.

Reduced Discrimination in the Tritanopic Confusion Line for Congenital Color Deficiency Adults.

In congenital color blindness the red-green discrimination is impaired resulting in an increased confusion between those colors with yellow. Our post-receptoral physiological mechanisms are organized in two pathways for color perception, a red-green (protanopic and deuteranopic) and a blue-yellow (tritanopic). We argue that the discrimination losses in the yellow area in congenital color vision deficiency subjects could generate a subtle loss of discriminability in the tritanopic channel considering discrepancies with yellow perception. We measured color discrimination thresholds for blue and yellow of tritanopic channel in congenital color deficiency subjects. Chromaticity thresholds were measured around a white background (0.1977 u', 0.4689 v' in the CIE 1976) consisting of a blue-white and white-yellow thresholds in a tritanopic color confusion line of 21 congenital colorblindness subjects (mean age = 27.7; SD = 5.6 years; 14 deuteranomalous and 7 protanomalous) and of 82 (mean age = 25.1; SD = 3.7 years) normal color vision subjects. Significant increase in the whole tritanopic axis was found for both deuteranomalous and protanomalous subjects compared to controls for the blue-white (F 2,100 = 18.80; p < 0.0001) and white-yellow (F 2,100 = 22.10; p < 0.0001) thresholds. A Principal Component Analysis (PCA) found a weighting toward to the yellow thresholds induced by deuteranomalous subjects. In conclusion, the discrimination in the tritanopic color confusion axis is significantly reduced in congenital color vision deficiency compared to normal subjects. Since yellow discrimination was impaired the balance of the blue-yellow channels is impaired justifying the increased thresholds found for blue-white discrimination. The weighting toward the yellow region of the color space with the deuteranomalous contributing to that perceptual distortion is discussed in terms of physiological mechanisms.

Contrasting effects of transcranial direct current stimulation on central and peripheral visual fields.

Recent research suggested that transcranial direct current stimulation (tDCS) can affect visual processing and that it can be useful in visual rehabilitation. Nevertheless, there are still few investigations on the subject. tDCS selectivity and the extent of its outcomes on visual perception are still to be assessed. Here, we investigate whether central and peripheral visual fields are equally affected by tDCS. We also tried to reproduce a previous work that has evaluated tDCS effects on the central visual field only (Kraft et al. 207:283-290, 2010). Fifteen healthy subjects participated in this randomized repeated-measure design study and received 1.5-mA anodal, cathodal and sham stimulation in different sessions, while performing 10-2 and 60-4 protocols in an automated perimeter. Anodal tDCS significantly decreased thresholds, but was limited to the most eccentric regions of the visual field measured (60°). This suggests that tDCS might be used for rehabilitation of peripheral visual field losses. We did not replicate the excitatory tDCS effect in the central visual field as previously reported by another group. Instead, we observed a trend toward an inhibitory (yet not statistically significant) effect of anodal tDCS on the central field. This might be explained by methodological differences. These results highlight that although tDCS is a technique with a low focality in the spatial domain, its effects might be highly focal in a functional domain. When taken together with previous findings, this also suggests that tDCS may have a differential effect on different retinotopic areas in the brain.

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.

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.

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.

Intraocular straylight and contrast sensitivity after contralateral wavefront-guided LASIK and wavefront-guided PRK for myopia.

PURPOSE: To compare intraocular straylight measurements and contrast sensitivity after wavefront-guided LASIK (WFG LASIK) in one eye and wavefront-guided photorefractive keratectomy (WFG PRK) in the fellow eye for myopia and myopic astigmatism correction. METHODS: A prospective, randomized study of 22 eyes of 11 patients who underwent simultaneous WFG LASIK and WFG PRK (contralateral eye). Both groups were treated with the NIDEK Advanced Vision Excimer Laser System, and a microkeratome was used for flap creation in the WFG LASIK group. High and low contrast visual acuity, wavefront analysis, contrast sensitivity, and retinal straylight measurements were performed preoperatively and at 3, 6, and 12 months postoperatively. A third-generation straylight meter, C-Quant (Oculus Optikgeräte GmbH), was used for measuring intraocular straylight. RESULTS: Twelve months postoperatively, mean uncorrected distance visual acuity was -0.06 +/- 0.07 logMAR in the WFG LASIK group and -0.10 +/- 0.10 logMAR in the WFG PRK group. Mean preoperative intraocular straylight was 0.94 +/- 0.12 logs for the WFG LASIK group and 0.96 +/- 0.11 logs for the WFG PRK group. After 12 months, the mean straylight value was 1.01 +/- 0.1 log s for the WFG LASIK group and 0.97 +/- 0.12 log s for the WFG PRK group. No difference was found between techniques after 12 months (P = .306). No significant difference in photopic and mesopic contrast sensitivity between groups was noted. CONCLUSIONS: Intraocular straylight showed no statistically significant increase 1 year after WFG LASIK and WFG PRK. Higher order aberrations increased significantly after surgery for both groups. Nevertheless, WFG LASIK and WFG PRK yielded excellent visual acuity and contrast sensitivity performance without significant differences between techniques.

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 mug/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 microg/g creatinine for patients compared with 0.5 +/- 0.5 microg/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.