Ana Laura de Araújo Moura

Toward a clinical protocol for assessing rod, cone, and melanopsin contributions to the human pupil response.

PURPOSE. To better understand the relative contributions of rod, cone, and melanopsin to the human pupillary light reflex (PLR) and to determine the optimal conditions for assessing the health of the rod, cone, and melanopsin pathways with a relatively brief clinical protocol. METHODS. PLR was measured with an eye tracker, and stimuli were controlled with a Ganzfeld system. In experiment 1, 2.5 log cd/m(2) red (640 ± 10 nm) and blue (467 ± 17 nm) stimuli of various durations were presented after dark adaptation. In experiments 2 and 3, 1-second red and blue stimuli were presented at different intensity levels in the dark (experiment 2) or on a 0.78 log cd/m(2) blue background (experiment 3). Based on the results of experiments 1 to 3, a clinical protocol was designed and tested on healthy control subjects and patients with retinitis pigmentosa and Lebers congenital amaurosis. RESULTS. The duration for producing the optimal melanopsin-driven sustained pupil response after termination of an intense blue stimulus was 1 second. PLR rod- and melanopsin-driven components are best studied with low- and high-intensity flashes, respectively, presented in the dark (experiment 2). A blue background suppressed rod and melanopsin responses, making it easy to assess the cone contribution with a red flash (experiment 3). With the clinical protocol, robust melanopsin responses could be seen in patients with few or no contributions from the rods and cones. CONCLUSIONS. It is possible to assess the rod, cone, and melanopsin contributions to the PLR with blue flashes at two or three intensity levels in the dark and one red flash on a blue background.

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.

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°, 15° and 21° 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.

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.

ON and OFF electroretinography and contrast sensitivity in Duchenne muscular dystrophy.

PURPOSE The study investigated possible asymmetric dysfunction of the ON and OFF visual mechanisms in DMD (Duchenne muscular dystrophy) patients associated with specific genetic alterations. METHODS nineteen DMD patients and 7 heterozygous dmd carriers were tested, as well as 19 age-matched controls.Full-field ergs were recorded using mesopic (1 cd/m(2)) and photopic (250 cd/m(2)) sawtooth luminance modulations as stimuli: rapid increase and ramping decrease (to isolate ON responses) or rapid decrease and ramping increase (for OFF responses). In addition, a psychophysical study comprised contrast sensitivity tests using two checkerboard stimuli at either higher (ON) or lower (OFF) luminance relative to the background: 0.3 cycles per degree (cpd) presented for 33 ms (low spatial frequency, short duration) and 2 cpd presented for 1500 ms (high spatial frequency, long duration). RESULTS A significant ERG amplitude reduction, relative to controls, was detected in the DMD patients in the mesopic positive peaks for both ON and OFF stimuli, as well as for the photopic ON stimulus (P < 0.05). Contrast sensitivity was significantly lower in the DMD patients (P < 0.05) relative to controls for the ON stimuli. Neither the ERG nor the contrast sensitivities were altered in the carriers. CONCLUSIONS This study suggests that there are ON and OFF ERG alterations when both rods and cones contribute to the ERG responses in DMD patients. When only cones are activated there is an asymmetrical ERG alteration, also revealed by the contrast sensitivity measurements.

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.

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

&NA; 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 10 cd/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. HighlightsUse of pupillometry to measure ANS response in mercury exposed patients is proposed.Comparison between cognitive damage and ANS response.Sympathetic response seemed to be impaired.