Influence of macular pigment on the sensitivity to discomfort glare from daylight.

Understanding the factors that influence the human perception of glare is necessary to properly address glare risks in buildings and achieve comfortable visual environments, especially in the workplace. Yet large inter-individual variabilities in glare perception remain unexplained and thus uncovered by the current empirical glare models. We hypothesize that this variability has an origin in the human retina, in particular in the density of macular pigments present in its central area, which varies between individuals. Macular pigments are known to absorb blue light and attenuate chromatic aberration, thus reducing light scatter. This study presents the outcomes of the first experiment ever conducted in a daylit office environment, in which glare sensitivity and macular pigment density were measured and compared for 110 young healthy individuals, along with other ocular parameters. The participants were exposed to different glare conditions induced by the sun filtered through either color-neutral or blue-colored glazing. In neutral daylight conditions with sun disc in the near periphery, neither macular pigment nor any other investigated ocular factors have an impact on discomfort glare perception whereas glare perception in conditions with the blue-colored sun disc in the near periphery was found to be correlated with macular pigment optical density.

Terson Syndrome: Not to Be Missed in Patients with Disorders of Consciousness.

The diagnosis of clinical cognitive motor dissociation (cCMD) can be hindered by pitfalls during standardized clinical evaluation based on gold-standard neurobehavioral rating scales. We introduce here a new pitfall, by reporting two cases of Terson syndrome (TS) after subarachnoid haemorrhage (SAH) caused by the rupture of an anterior communicant artery aneurysm, hospitalized in the Acute Neurorehabilitation Unit (ANR) of CHUV. TS is reported to occur in 8-19.3% of patients suffering from SAH. It can lead to significant visual impairment and if unrecognized, may impair the patient's capacity to interact appropriately with the environment; it thus presents an important pitfall in recognizing clinical cognitive-motor dissociation (cCMD) in patients with altered states of consciousness. An early ophthalmological exam should be considered in all patients with SAH and disorders of consciousness or visual complaints.

Pathogenesis of Vascular Retinal Manifestations in COVID-19 Patients: A Review.

Pandemic infection secondary to coronavirus disease 2019 (COVID-19) had an important impact on the general population affecting not only respiratory tract but also many other organs. Ocular manifestations are quite common at the level of the anterior segment (conjunctivitis, dry eye), while posterior segment and, in particular, retinal findings are less frequent. In the retina, COVID-19 is associated with vascular events. Since retinal arteries and veins represent an accessible window to the microvasculature of the rest of the body, a better understanding of the profile of retinal vascular occlusive events may help elucidate mechanisms of thrombo-occlusive complications in other organs in patients affected by COVID-19. In this review, we conducted a systematic literature search focused on retinal arterial and/or retinal venous manifestations. Twenty-one studies were included, describing a wide range of manifestations from mild signs like cotton wool spots, focal and flame-shaped hemorrhages, and vein dilation to more severe retinal artery and vein occlusions. Two principal pathogenetic mechanisms are considered responsible for these complications: a hypercoagulative state and a massive inflammatory response leading to a disseminated intravascular coagulation-like syndrome.

Susac Syndrome: A Case Series.

BACKGROUND: Susac syndrome (SS) is an autoimmune disorder that involves the eyes, the brain, and the ears. It is a rare cause of recurrent branch retinal artery occlusion. The purpose of this study was to report cases of SS, highlighting the clinical presentations, therapeutic options, and their outcome. PATIENTS AND METHODS: Retrospective case series of patients seen at our institution for SS between 2005 and 2020. Demographics, clinical characteristics, treatment, and outcome were studied. RESULTS: Four patients (3 females, mean age 29 years old) were included in the study. According to the recently revised diagnostic criteria, three patients had definite and one patient had probable SS (distinctive ophthalmological and brain involvement without ear involvement). Initial visual acuity (VA) was normal in all eyes, but two patients had unilateral visual field impairment. Gass plaques (defined as yellow-white plaques found in the arteriolar wall away from arterial bifurcations) were observed on fundus examination in all patients. Fluorescein angiography revealed arteriolar wall hyperfluorescence and branch retinal arterial occlusions (BRAOs) in the absence of other signs of intraocular inflammation in all patients. Initial treatment consisted of a high-dose corticosteroid (intravenous or oral) with additional immunosuppressive therapy (azathioprine, intravenous immunoglobulins, mycophenolate mofetil, and/or cyclophosphamide). Residual symptoms were present in all patients and included scotoma (n = 2) and hearing loss (n = 3). CONCLUSION: SS is a rare disease with characteristic ophthalmological manifestation. The majority of patients present a crude form of the triad, and retinal findings may be the first initial manifestation. Ophthalmologists should consider the possibility of an SS in all young patients presenting with BRAOs.

Quantification of the early pupillary dilation kinetic to assess rod and cone activity.

Rods, cones and melanopsin contribute in various proportions, depending on the stimulus light, to the pupil light response. This study used a first derivative analysis to focus on the quantification of the dynamics of pupillary dilation that immediately follows light-induced pupilloconstriction in order to identify novel parameters that reflect rod and cone activity. In 18 healthy adults, the pupil response to a 1 s blue light stimulus ranging from - 6.0 to 2.65 log cd/m2 in dark-adapted conditions and to a 1 s blue light stimulus (2.65 log cd/m2) in light-adapted conditions was recorded on a customized pupillometer. Three derivative parameters which describe the 2.75 s following the light onset were quantified: dAMP (maximal amplitude of the positive peak), dLAT (latency of the positive peak), dAUC (area under the curve of the positive peak). We found that dAMP and dAUC but not dLAT have graded responses over a range of light intensities. The maximal positive value of dAMP, representing maximal rate of change of early pupillary dilation phase, occurs at - 1.0 log cd/m2 and this stimulus intensity appears useful for activating rods and cones. From - 0.5 log cd/m2 to brighter intensities dAMP and dAUC progressively decrease, reaching negligible values at 2.65 log cd/m2 indicative of a melanopsin-driven pupil response that masks the contribution from rods and cones to the early phase of pupillary dilation.

Case Report: A Novel Mutation in the Mitochondrial MT-ND5 Gene Is Associated With Leber Hereditary Optic Neuropathy (LHON).

Leber hereditary optic neuropathy (LHON) is a mitochondrial disease causing severe bilateral visual loss, typically in young adults. The disorder is commonly caused by one of three primary point mutations in mitochondrial DNA, but a number of other rare mutations causing or associated with the clinical syndrome of LHON have been reported. The mutations in LHON are almost exclusively located in genes encoding subunits of complex I in the mitochondrial respiratory chain. Here we report two patients, a mother and her son, with the typical LHON phenotype. Genetic investigations for the three common mutations were negative, instead we found a new and previously unreported mutation in mitochondrial DNA. This homoplasmic mutation, m.13345G>A, is located in the MT-ND5 gene, encoding a core subunit in complex I in the mitochondrial respiratory chain. Investigation of the patients mitochondrial respiratory chain in muscle found a mild defect in the combined activity of complex I+III. In the literature six other mutations in the MT-ND5 gene have been associated with LHON and by this report a new putative mutation in the MT-ND5 can be added.

Update in the Management of Idiopathic Intracranial Hypertension.

Idiopathic intracranial hypertension is a syndrome of increased intracranial pressure of unknown cause that most often occurs in women of childbearing age. Most patients are overweight or obese with a history of recent weight gain. Following a brief review of the symptoms and signs, we discuss the approach to assessment and monitoring of this condition. We then present a practical approach to treatment. Because patients frequently struggle with weight loss and can also have refractory headaches and coexisting psychosocial issues, we emphasize the importance of a multidisciplinary approach to the management of this common condition.

Early-Stage Alzheimer's Disease Does Not Alter Pupil Responses to Colored Light Stimuli.

BACKGROUND: Pathologic changes in cerebral and retinal structures governing the pupillary light reflex occur in Alzheimer's disease (AD). Analysis of pupillary responses originating from different retinal cells may allow for non-invasive detection of cerebral AD pathology. OBJECTIVE: This study aimed to quantify the pupil light reflex using a portable chromatic pupillometer in patients with early stage AD and compare their responses to those of a healthy control group. METHODS: Participants in this case-control pilot study were recruited from a well-characterized cohort of elderly people participating in a larger prospective study on early AD. Cognitive testing, volumetric brain imaging, and lumbar puncture were performed in all participants to define two groups: early AD, i.e., cognitively impaired subjects with biomarker-confirmed AD pathology, and control group of subjects with normal cognition and normal CSF biomarker profile. Pupil responses to red and blue light stimuli intended to activate cone photoreceptors and melanopsin ganglion cells were recorded under photopic conditions. RESULTS: Sixteen patients with AD (mean age 77 years) and sixteen controls (mean age 71 years) were tested. Baseline pupil size was significantly smaller in AD patients. Pupillary contraction amplitude to all red and blue lights was also smaller in AD patients but did not reach statistical significance. The post-illumination pupillary response was the same between the two groups. CONCLUSION: Compared to healthy controls, we found only a smaller resting size of the pupil in patients with early AD. The pupillary dynamics to light stimulation remained relatively preserved.

Can Extra Daytime Light Exposure Improve Well-Being and Sleep? A Pilot Study of Patients With Glaucoma.

Glaucoma damages retinal ganglion cells, including intrinsically photosensitive retinal ganglion cells (ipRGCs). These cells modulate various non-visual physiological and psychological functions which are modulated by light. In patients with glaucoma, we assessed the effect of daily bright light exposure (LE) on several melanopsin-dependent functions, such as the pupil constriction, circadian rest-activity cycles, sleep and subjective well-being including relaxation, alertness and mood. Twenty patients participated in the study (9 women, 11 men, mean age = 67.6 ± 7.5 y). Pupillometry was performed before the LE weeks and repeated on the last day of LE. The post-illumination pupil response (PIPR) was calculated as a proxy for melanopsin-dependent activation. Participants continuously wore an activity monitor and self-assessed sleep quality, well-being and visual comfort for 7 days before and during 4 weeks of daily bright LE (30 min to 10,000 lux polychromatic bright white light). After the LE, there was a significantly greater PIPR and higher subjective sleep quality when compared to the pre-LE week (p < 0.05), but no significant changes in 24-h rhythms or sleep parameters. A greater PIPR was correlated with an increase in circadian amplitude and higher inter-daily stability (derived from rest-activity cycles; p < 0.05). In a small group of patients with glaucoma, scheduled daily bright light exposure could improve subjective sleep quality. These findings highlight the importance to evaluate and maintain non-visual functions at different levels in patients with progressive loss of ipRGCs.

The Tadpole Pupil: Case Series With Review of the Literature and New Considerations.

Tadpole pupil is a rare phenomenon in which segmental spasm of the iris dilator muscle results in a tadpole-shaped pupil. The pupillary distortion is usually unilateral, lasts several minutes, and can recur in clusters. Any segment of the iris can be affected; thus, for some patients, a different-shaped tadpole pupil is noticed from episode to episode. Tadpole pupil most commonly appears spontaneously in young women. Tadpole pupil is not associated with any systemic disorders, but an ipsilateral Horner syndrome is noted in 46% of patients. In this article, we have reviewed the existing literature of tadpole pupil, compiling all the published cases in a table and reporting four additional cases to re-examine the clinical profile of this disorder and to consider the different purported mechanisms as means to understand its possible etiology and treatment. The common denominator in the pathophysiology of tadpole pupil is a focal excessive contraction (segmental spasm) of the iris dilator muscle. Based on various proposed pathophysiologic mechanism of tadpole pupil, we can consider potential forms of treatment.

Maturation of the Pupil Light Reflex Occurs Until Adulthood in Mice.

With respect to photoreceptor function, it is well known that electroretinogram (ERG) amplitudes decrease with age, but to our knowledge, studies describing age-related changes in the pupil light response (PLR) of mice are lacking. This study recorded the PLR and ERG in C57BL/6 and Sv129S6 wild-type mice at three different ages during early adulthood. Dark- and light-adapted PLR and ERG measurements were performed at 1, 2, and 4 months of age. For PLR measurements, we used either a red (622 nm) or blue (463 nm) light stimulus (500 ms) to stimulate one eye. We selected various light intensities ranging across almost 4 log units and subsequently classified them as low, medium, or high intensity. From the recorded PLR, we selected parameters to quantify the early and late phases of the response such as the baseline pupil size, the maximal constriction amplitude, the maximal velocity, the early partial dilation (area under the curve of the positive peak of the first derivative of PLR tracing), and the sustained constriction amplitude. For ERG measurements, both scotopic and photopic responses were recorded following stimulation with green light (520 nm) at preselected intensities. The amplitudes and latencies of the a-wave and the b-wave were also analyzed. In both strains, 1-month-old animals presented with a smaller baseline pupil diameter compared to that in 2- and 4-month-old mice. They also exhibited greater maximal constriction amplitude in response to red stimuli of medium intensity. Further, 1-month-old Sv129S6 mice responded with greater constriction amplitude to all other red and blue stimuli. One-month-old C57BL/6 mice also demonstrated faster early partial dilation and smaller sustained response to low blue stimuli. The ERG of 1-month-old C57BL/6 mice showed a greater scotopic a-wave amplitude compared to that of 2-month-old mice, whereas no significant differences were found in Sv129S6 mice. These results suggest that the functional maturation of the neuronal pathway that mediates the PLR continues after 1 month of age. In studies that measure PLR to determine retinal integrity in adult mice, it is thus important to determine normative values in animals of 2 months of age.

Chromatic Pupillometry in Children.

Chromatic pupillometry is a technique that is increasingly used to assess retinal disorders. As age may be one of the various factors which can influence the pupillary light reaction, this study aimed to evaluate the pupil responses to colored light stimuli in the pediatric population. Fifty-three children with normal vision and without any history of ocular disorders were tested with a portable pupillometer. Four test sequences were used: five dim blue (470 nm) stimuli presented in half log steps ranging from -3.15 to -1.15 log cd/m2 after 3 min of dark adaptation, five red (622 nm) stimuli of -1.15, -0.7, -0.15, 0.3, and 0.85 log cd/m2 after 1 min light adaptation, one bright blue stimulus of 2.2 log cd/m2 and one bright red of 2 log cd/m2. The results were grouped by age: a younger group included 27 children aged from 3 to 10 years old and an older group included 26 from 10 and 1 month to 18 years old. The younger group had a smaller pupil diameter after dark adaptation compared with the older group. A linear regression defining the photopic threshold showed that younger subjects had a higher threshold, e.g., needed a brighter red stimulus to evoke a threshold pupil response comparable that of subjects. Age thus seems to influence outer retinal sensitivity at least as evaluated by the pupillary photopic threshold intensity. The post-illumination pupillary reaction was used as a marker of intrinsic melanopsin activity and did not show any difference between the two age groups.

Distinct modes of stress granule assembly mediated by the KH-type RNA-binding protein Rnc1.

We have previously identified the KH-type RNA-binding protein Rnc1 as an important regulator of the posttranscriptional expression of the MAPK phosphatase Pmp1 in fission yeast. Rnc1 localization in response to stress has not been elucidated thus far. Here, we report the dual roles of Rnc1 in assembly of stress granules (SGs), nonmembranous cytoplasmic foci composed of messenger ribonucleoproteins. Rnc1 can localize to poly(A)-binding protein (Pabp)-positive SGs upon various stress stimuli, including heat shock (HS) and arsenite treatment. Furthermore, Rnc1 deletion results in decreased SGs, indicating that Rnc1 is a new component and a regulator of SGs. Notably, Rnc1 translocates to the dot-like structures faster than Pabp, and this stress-induced Rnc1 translocation does not require its RNA-binding ability, as the Rnc1KH1,2,3GD mutant protein with impaired RNA-binding activity forms dots rather more efficiently than the wild-type Rnc1 upon HS. Interestingly, in the absence of stress, Rnc1 overproduction induced massive aggregation of Pabp-positive SGs and eIF2α phosphorylation. In clear contrast, overproduction of the Rnc1KH1,2,3GD mutant failed to induce Pabp aggregation and eIF2α phosphorylation, indicating that Rnc1 overproduction-induced SG assembly requires Rnc1 RNA-binding activity. Collectively, Rnc1 regulates SG assembly, dependently or independently of its RNA-binding activity.

Invited Commentary: Evaluation of Horner Syndrome in the MRI Era.

This Invited Commentary discusses the following article: BACKGROUND:: To identify the etiologies of adult Horner syndrome (HS) in the MRI era using a targeted evaluation approach and to assess the value and yield of targeted imaging. METHODS: A retrospective chart review was performed of 200 adult outpatients with HS, confirmed with cocaine eyedrop testing. Patients were divided into subgroups based on the presence or absence of symptoms and those who did or did not receive additional testing with hydroxyamphetamine drops. Imaging was obtained based on pharmacologic localization and/or clinical evaluation. The etiology of HS and the yield of imaging were determined in all subgroups. RESULTS: Imaging showed causative lesions in 24 of 179 (12.84%) imaged patients with HS, and 13 (69.0%) were determined "idiopathic." Of the patients who underwent testing with hydroxyamphetamine drops (132 patients), 86 had a postganglionic localization with an imaging yield of 8.1%, and 46 had preganglionic cause with an imaging yield of 21.7%. Fifty-three patients (26.5%) never noticed ptosis/anisocoria before examination, and the imaging yield in this subgroup was 2.8%. Eighteen of the 200 patients (9.0%) had serious pathology, including carotid artery dissection, brain, or neck mass, and 6 of these (31.6%) had acute symptoms and/or pain. CONCLUSION: HS is most often idiopathic with serious pathology being relatively infrequent. When determining etiology, the absence of symptoms is not predictive of the pathology. However, acute onset of symptoms and/or pain are possible indicators for serious pathology. Localizing the lesion using hydroxyamphetamine drops whenever obtainable and available is still an efficient way to target imaging evaluation.