ArticleLiterature Review

Diagnosis, Pathophysiology and Treatment of Photophobia

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Abstract

Photophobia, an abnormal intolerance to light, is associated with a number of ophthalmic and neurologic conditions. In the presence of normal neurologic and ophthalmologic examinations, the most common conditions associated with photophobia are migraine, blepharospasm, and traumatic brain injury. Recent evidence indicates that the intrinsically photosensitive retinal ganglion cells play a key role in the pathophysiology of photophobia. Although pharmacologic manipulation of intrinsically photosensitive retinal ganglion cells and the neural pathways that mediate photophobia may be possible in the future, current therapies are directed at the underlying cause of the photophobia and optical modulation of these cells and pathways.

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... Although occasionally reported in isolation, photosensitivity is commonly seen in patients with PTH and is frequently associated with migraine-type headaches. 23 The primary difference between PTH and migraine is that the PTH is initiated from an mTBI, whereas the migraine is possibly initiated by chemical imbalances, nerve communication errors, and blood vessel damage and can be triggered by hormonal, emotional, or physical causes. 24 Similarities, however, between the classic migraine and PTH include headache, nausea, dizziness, insomnia, and many more diverse symptoms. ...
... 54 Of interest, certain features are shared between TBI and DES, including predilection to light sensitivity. 17,23,54,59 Therefore, when patients with TBI present with eye pain in the absence of ocular surface damage or tear film disruption, clinicians should consider the possibility of NOP. ...
... Such ipRGC axons project to the OPN, which then lead downstream to the SSN causing ocular vasodilation and activation of ocular trigeminal afferents, which are heavily expressed in blood vessels (figure, D). 60,61 These afferents further project to the trigeminal nucleus and function in the relaying of sensory information to the face that in response to light and pain stimuli. 23,60 Sleep disturbance in subjects with mTBI ...
Article
The majority of traumatic brain injury (TBI) patients are classified as having a mild traumatic brain injury (mTBI). Despite being categorized as mild, these individuals report ongoing and complex symptoms, which negatively affects their ability to complete activities of daily living and overall quality of life. Some of the major symptoms include anxiety, depression, sleep problems, headaches, light sensitivity, and difficulty reading. The root cause for these symptoms is under investigation by many in the field. Interestingly, several of these symptoms such as headaches, ocular pain, light-sensitivity, and sleep disturbances may overlap and share underlying circuitry influenced by the intrinsically photosensitive retinal ganglion cells (ipRGCs). These cells are light-sensing, but non-image forming, and they influence corneal function, pupillary constriction, and circadian rhythm. In this review, we discuss these symptoms and propose a role of the ipRGCs as at least one underlying and unifying cause for such symptomology.
... Through the pterygopalatine ganglion, this causes ocular vasodilation and activation of ocular trigeminal afferents through the trigemino-autonomic reflex [85]. These afferents then project to the trigeminal nucleus caudalis, the thalamus, and to the cortex [85,86]. The trigeminal system is key in the pathophysiology of photophobia as it is very closely linked to pain sensation [85]. ...
... These cells, also through the optic nerve, project directly to the thalamus which is also receiving intracranial nociceptive input. The thalamus receives light and pain information, which is then projected to sensory and association cortices [85,86]. The pathway involving the thalamus is particularly interesting because of the role of the thalamus for multiple sensory integration [85,86]. ...
... The thalamus receives light and pain information, which is then projected to sensory and association cortices [85,86]. The pathway involving the thalamus is particularly interesting because of the role of the thalamus for multiple sensory integration [85,86]. This pathway could explain the photophobia seen in patients with meningitis or sub-arachnoid hemorrhage [85]; -The third pathway also involves intrinsically photosensitive regular ganglion cells, but through projections that do not involve the optic nerve. ...
Chapter
Photosensitivity or “visual sensitivity” is in the literature used in different ways: (1) the focal or generalized epileptiform EEG reaction to Intermittent Photic Stimulation (IPS) or other visual stimuli, so called photoparoxysmal response or PPR; (2) visual stimuli that provoke seizures in everyday life, such as flickering sunlight, TV, videogames or striped patterns; and (3) sensitivity to lights in terms of ocular discomfort or photophobia. The variability in photic driving as physiological visual evoked responses has intrigued scientists since the use of IPS in EEG clinical research and gave insight into pathophysiological mechanisms.
... 8,12,14,15,18,21 Photophobia in mTBI or Concussion Photophobia, or photosensitivity, is defined as an abnormal tolerance to light or visual discomfort in the presence of normal light levels. [40][41][42] Although occasionally reported in isolation, photophobia is commonly seen in patients with PTH and commonly associated with migraine-type headaches. 41 Tension-type headache sufferers also report more sensitivity to light compared with controls. ...
... [40][41][42] Although occasionally reported in isolation, photophobia is commonly seen in patients with PTH and commonly associated with migraine-type headaches. 41 Tension-type headache sufferers also report more sensitivity to light compared with controls. 40 Photophobia is an increased sensitivity to light and visual stimuli from all sources. ...
... Patients tend to be particularly sensitive to artificial indoor light, computer monitors including screens of all kind and glare. 41 Screen intolerance is particularly important given its omnipresence and patients will often dim the light intensity of the screen or modify the hue. 43 This may be due to the rate at which computer or cell phone screens refresh (60 Hz) with concussed individuals having a higher critical flicker frequency threshold. ...
Article
The most common symptom of post-concussive syndrome (PCS) is post-traumatic headache (PTH) accompanied by photophobia. Post-traumatic headache is currently categorized as a secondary headache disorder with a clinical phenotype described by its main features and resembling one of the primary headache disorders: tension, migraine, migraine-like cluster. Although PTH is often treated with medication used for primary headache disorders, the underlying mechanism for PTH has yet to be elucidated. The goal of this narrative literature review is to determine the current level of knowledge of these PTHs and photophobia in mild traumatic brain injury (mTBI) in order to guide further research and attempt to discover the underlying mechanism to both symptoms. The ultimate purpose is to better understand the pathophysiology of these symptoms in order to provide better and more targeted care to afflicted patients. A review of the literature was conducted using the databases CINAHL, EMBASE, PubMed. All papers were screened for sections on pathophysiology of PTH or photophobia in mTBI patients. Our paper summarizes current hypotheses. Although the exact pathophysiology of PTH and photophobia in mTBI remains to be determined, we highlight several interesting findings and avenues for future research, including central and peripheral explanations for PTH, neuroinflammation, cortical spreading depolarization and the role of glutamate excitotoxicity. We discuss the possible neuroanatomical pathways for photophobia and hypothesize a possible common pathophysiological basis between PTH and photophobia.
... El dolor neuropático se define como el «dolor iniciado o causado por una lesión o disfunción primaria del sistema nervioso» 4 , puede ocurrir en la córnea, ya que es la estructura con más inervación del cuerpo 4 , así como por afectación de otras estructuras oculares. Cursa con dolor, irritación ocular, sensación de sequedad y fotofobia [5][6][7][8][9][10] . ...
... Podemos definir la fotofobia como la intolerancia anormal a la luz [5][6][7] . En oftalmología hay muchas enfermedades que pueden cursar con fotofobia: ojo seco, conjuntivitis, uveítis, epiescleritis, el uso de determinados fármacos oculares, cirugía de catarata o refractiva. ...
... En oftalmología hay muchas enfermedades que pueden cursar con fotofobia: ojo seco, conjuntivitis, uveítis, epiescleritis, el uso de determinados fármacos oculares, cirugía de catarata o refractiva. Los pacientes son sensibles a la luz en situaciones donde otras personas no lo serían, presentan una exploración oftalmológica normal, suelen buscar lugares pocos iluminados y suelen presentarse en la consulta con las gafas de sol puestas como le ocurre a nuestro paciente 5,7 . ...
Article
Full-text available
The case is presented of a 14 year-old patient diagnosed with Sudeck's syndrome secondary to uneventful foot trauma. The patient complained of decreased visual acuity along with photophobia and intense ocular pain not correlated with the exploratory findings. Sudeck's syndrome is an idiopathic neuropathic inflammatory disease characterised by disproportionate pain, unrelated to a previous traumatic event, which can evolve to severe and generalised pain. A new explanation has recently described this as "neuropathic eye pain" for those patients with severe eye pain that do not correlate with clinical signs. In the case presented here, the pain became widespread and led to photophobia and very intense ocular neuropathic pain. It is believed that this was the cause of the visual decrease presented by this patient. It is proposed that the Sudeck syndrome should become part of the differential diagnosis of neuropathic eye pain. Copyright © 2019 Sociedad Española de Oftalmología. All rights reserved.
... El dolor neuropático se define como el «dolor iniciado o causado por una lesión o disfunción primaria del sistema nervioso» 4 , puede ocurrir en la córnea, ya que es la estructura con más inervación del cuerpo 4 , así como por afectación de otras estructuras oculares. Cursa con dolor, irritación ocular, sensación de sequedad y fotofobia [5][6][7][8][9][10] . ...
... Podemos definir la fotofobia como la intolerancia anormal a la luz [5][6][7] . En oftalmología hay muchas enfermedades que pueden cursar con fotofobia: ojo seco, conjuntivitis, uveítis, epiescleritis, el uso de determinados fármacos oculares, cirugía de catarata o refractiva. ...
... En oftalmología hay muchas enfermedades que pueden cursar con fotofobia: ojo seco, conjuntivitis, uveítis, epiescleritis, el uso de determinados fármacos oculares, cirugía de catarata o refractiva. Los pacientes son sensibles a la luz en situaciones donde otras personas no lo serían, presentan una exploración oftalmológica normal, suelen buscar lugares pocos iluminados y suelen presentarse en la consulta con las gafas de sol puestas como le ocurre a nuestro paciente 5,7 . ...
Article
Full-text available
The case is presented of a 14 year-old patient diagnosed with Sudeck's syndrome secondary to uneventful foot trauma. The patient complained of decreased visual acuity along with photophobia and intense ocular pain not correlated with the exploratory findings. Sudeck's syndrome is an idiopathic neuropathic inflammatory disease characterized by disproportionate pain, unrelated to a previous traumatic event, which can evolve to severe and generalized pain. A new explanation has recently been described this as “neuropathic eye pain” for those patients with severe eye pain that do not correlate with clinical signs. In the case presented here, the pain became widespread and led to photophobia and very intense ocular neuropathic pain. It is believed that this was the cause of the visual decrease that presented by this patient. It is proposed that the Sudeck syndrome should become part of the differential diagnosis of neuropathic eye pain.
... Various pathologies that may induce photophobia can be ocular (e.g., dry eye, uveitis, cone dystrophy), neurologic (e.g., optic neuritis, demyelinating disorders, migraine), or medication-related (e.g., lithium, benzodiazepines, chloroquine) in origin, among many other ailments (e.g., intracranial neoplasm, zinc deficiency). 6,10 Additionally, the notion that optical filters may have clinical potential in the treatment of photophobia is supported by many patients experiencing photophobic symptoms after cataract surgery. The appearance of photophobic symptoms after the removal of a patient's intrinsic light filter may suggest that a filter could be added to mitigate these same symptoms. ...
... Though photophobia has been reported in patients with attention deficit hyperactivity disorder (ADHD), panic disorder, 26,27 agoraphobia, 26 anxiety, and depression, 6 it is usually accompanied by additional pathology that may be contributing to the photophobia. 6 Patients with agoraphobia have shown symptomatic improvement in photophobia after cognitive behavioral therapy. ...
... Though photophobia has been reported in patients with attention deficit hyperactivity disorder (ADHD), panic disorder, 26,27 agoraphobia, 26 anxiety, and depression, 6 it is usually accompanied by additional pathology that may be contributing to the photophobia. 6 Patients with agoraphobia have shown symptomatic improvement in photophobia after cognitive behavioral therapy. 26 This suggests that their photophobia is likely related to their psychiatric illness as opposed to an external process. ...
... El dolor neuropático se define como el «dolor iniciado o causado por una lesión o disfunción primaria del sistema nervioso» 4 , puede ocurrir en la córnea, ya que es la estructura con más inervación del cuerpo 4 , así como por afectación de otras estructuras oculares. Cursa con dolor, irritación ocular, sensación de sequedad y fotofobia [5][6][7][8][9][10] . ...
... Podemos definir la fotofobia como la intolerancia anormal a la luz [5][6][7] . En oftalmología hay muchas enfermedades que pueden cursar con fotofobia: ojo seco, conjuntivitis, uveítis, epiescleritis, el uso de determinados fármacos oculares, cirugía de catarata o refractiva. ...
... En oftalmología hay muchas enfermedades que pueden cursar con fotofobia: ojo seco, conjuntivitis, uveítis, epiescleritis, el uso de determinados fármacos oculares, cirugía de catarata o refractiva. Los pacientes son sensibles a la luz en situaciones donde otras personas no lo serían, presentan una exploración oftalmológica normal, suelen buscar lugares pocos iluminados y suelen presentarse en la consulta con las gafas de sol puestas como le ocurre a nuestro paciente 5,7 . ...
... In migraine, mechanisms likely involve hypersensitivity of the intrinsically photosensitive retinal ganglion cells that may project to pain processing regions of the thalamus, and hypersensitivity, structural remodeling, and altered functional connectivity of visual processing regions in the brain. [26][27][28][29] Functional and structural brain imaging studies in PPTH are required to determine if there are similar findings in PPTH. Furthermore, photosensitivity is considered a relatively common symptom of mTBI, even in the absence of PTH. 30 However, in a study of 447 soldiers with mTBI, those with PTH (n ¼ 198) were more likely to have photophobia compared with soldiers who had mTBI but no PTH (62.7% vs. 49.3%, ...
... 19 Further research is needed to determine the extent to which photosensitivity following mTBI is due to the TBI itself versus being associated with PTH. 28 Hyperacusis symptoms were more severe in those with PPTH compared to migraine in this study. Although it is quite likely that hyperacusis symptom severity in PPTH is at least similar to that found in migraine, further studies are needed to determine if in fact they are more severe in PPTH. ...
Article
Full-text available
Background and Objective Symptoms of persistent post-traumatic headache (PPTH) most often resemble those of migraine, including the presence of photo-, phono-, and cutaneous hypersensitivities. The severity of these hypersensitivity symptoms in those with PPTH compared to those with migraine has yet to be fully elucidated. The objective of this study was to compare symptoms of sensory hypersensitivities between PPTH, migraine, and healthy controls (HCs). Further defining characteristics of PPTH and its similarities to migraine might assist with developing future diagnostic criteria for PPTH and provide insights into PPTH mechanisms. Methods This analysis included 56 individuals with PPTH attributed to mild traumatic brain injury, 30 with migraine, and 36 HCs. To assess sensory hypersensitivities, all subjects completed the Allodynia Symptom Checklist-12, the Photosensitivity Assessment Questionnaire, and the Hyperacusis Questionnaire. Differences among groups were assessed using Fisher’s exact test, Kruskal–Wallis, or Mann–Whitney U test. Results PPTH and migraine groups had greater severity of cutaneous, photo-, and phono-hypersensitivity symptoms compared to HCs. There were no statistically significant differences between the PPTH and migraine groups for cutaneous allodynia (median [first quartile, third quartile]; PPTH: 4.0 [2.0, 7.0]; migraine: 5.0 [3.0, 8.0]; p = 0.54) or photosensitivity severity (PPTH: 5.0 [2.0, 7.0]; migraine: 5.0 [2.0, 6.0]; p = 0.53). Those with PPTH had higher hyperacusis scores compared to those with migraine (PPTH: 23.0 [17.0, 31.0]; migraine: 13.5 [9.0, 24.0]; p = 0.001). Conclusion Sensory hypersensitivity symptoms among individuals with PPTH are at least as severe as those experienced by people with migraine. Results further confirm symptom similarities between PPTH and migraine and could suggest that PPTH and migraine have a partially shared underlying pathophysiology.
... Other studies have reviewed neural pathways implicated in photophobia. [21][22][23] As such, we will concisely summarise several candidate pathways that have been identified (figure 1). ...
... Pathologic neuronal dysregulation likely underlies photophobia in DE, migraine and TBI In DE, migraine and TBI, the common denominator linking light to pain is the trigeminothalamic pathway. 23 When we touch a hot stove, acute nociceptive pain signals generate a withdrawal reflex that effectively removes our hand from the heat, although with accompanying pain. Under normal physiologic conditions, barring no tissue damage, withdrawal from the painful stimuli halts further nociceptive input and no additional pain is elicited. ...
Article
Background Photophobia is a potentially debilitating symptom often found in dry eye disease (DE), migraine and traumatic brain injury (TBI). Methods We conducted a review of the literature via a PubMed search of English language articles with a focus on how photophobia may relate to a shared pathophysiology across DE, migraine and TBI. Results DE, migraine and TBI are common conditions in the general population, are often comorbid, and share photophobia as a symptom. Across the three conditions, neural dysregulation of peripheral and central nervous system components is implicated in photophobia in various animal models and in humans. Enhanced activity of the neuropeptide calcitonin gene-related peptide (CGRP) is closely linked to photophobia. Current therapies for photophobia include glasses which shield the eyes from specific wavelengths, botulinum toxin, and inhibition of CGRP and its receptor. Many individuals have persistent photophobia despite the use of these therapies, and thus, development of new therapies is needed. Conclusions The presence of photophobia in DE, migraine and TBI suggests shared trigeminothalamic pathophysiologic mechanisms, as explained by central neuroplasticity and hypersensitivity mediated by neuropeptide CGRP. Treatment strategies which target neural pathways (ie, oral neuromodulators, transcutaneous nerve stimulation) should be considered in patients with persistent photophobia, specifically in individuals with DE whose symptoms are not controlled with traditional therapies.
... Post-concussion syndrome can develop after head trauma, even after mTBI, due to neurophysiological influences and psychological factors that may exaggerate or increase the persistence of chronic symptoms due to stressful life situations or depression. 1 Head trauma that induces a concussion or postconcussion syndrome is associated with various visual symptoms in 69-82% of patients. 11 Researchers suggest that trauma can lead to structural changes, irritation or injury to specific painsensitive areas in the brain that could be involved in increased light sensitivity and photophobia. Thus, the brain's ability to adjust to numerous different lights is diminished, which results in symptoms such as eye strain, headaches, and a lack of concentration. 1 Although photophobia is caused mainly by light, some blind patients have been documented to have photophobia. ...
... This is another explanation why these patients find the light brighter and more painful than non-injured individuals. 11 Optical filters have been utilised in the treatment of photophobia. Rose-coloured tinted lenses, referred to as FL-41 tinted lenses, were found to successfully reduce migraine frequency in over 50% of children. 1 These glasses effectively filter out the noxious blue-green light emitted by fluorescent lighting in the visible light spectrum. ...
Article
Full-text available
Photophobia is considered the second most common symptom of both concussion and post-concussion syndrome. Soldiers on duty experience photophobia after blast-related concussions or mild traumatic brain injury in 60–75% of instances. In addition, soldiers report other symptoms, such as asthenopia, squinting, dry eyes and headaches, for which they are considered to be at high risk. According to the International Brain Injury Association, some concussed patients report indirect symptoms such as multi-tasking difficulties, dizziness, vertigo, and fatigue. Moreover, some concussed individuals experience photophobia for approximately 6 months or indefinitely. We present the case of a 23-year-old soldier who presented with severe photophobia after a mild traumatic head injury. His photophobia was alleviated after the administration of topical anaesthetic drops in the eyes in the absence of any ocular surface pathology. He was diagnosed with post-concussion syndrome light sensitivity and was managed successfully with rose-coloured special photophobia glasses tinted with FL-41. Photophobia is a common neurological symptom in military personnel that needs more attention as it affects body and mind. We have reported an uncommon pathway of photophobia, which may unveil an unrecognised mechanism that may play a role in post-concussion photophobia.
... Photophobia is a common and debilitating symptom that describes painful sensitivity to light. It is often associated with migraine and other neurological disorders, but can also arise from ocular pathologies, psychiatric conditions, and as a pharmacological side effect (Albilali and Dilli, 2018;Katz and Digre, 2016;Noseda et al., 2018). Despite its common prevalence, photophobia remains poorly understood. ...
... With traditional retinal light transduction pathways, photophobia has been proposed to act through (1) rods and cones parasympathetically triggering ocular vasodilation, which in turn activate trigeminal nociceptive afferents in blood vessels, (Okamoto et al., 2010) or (2) cone pathways relaying light signals to nociceptive trigeminovascular thalamic neurons (Noseda et al., 2010). The common theme is the intersection of afferent visual processing with nociceptive trigeminal pathways (Katz and Digre, 2016;Noseda et al., 2018;Rosenthal and Borsook, 2012). ...
Article
Full-text available
Numerous pathologies can contribute to photophobia. When considering light transduction alone, photophobia may be triggered through melanopsin pathways (non-image forming), rod and cone pathways (image-forming), or some combination of the two. We evaluated a 39 year old female patient with longstanding idiopathic photophobia that was exacerbated by blue light, and tested her by presenting visual stimuli in an event-related fMRI experiment. Analysis showed significantly greater activation in bilateral pulvinar nuclei, associated with the melanopsin intrinsically photosensitive retinal ganglion cell (ipRGC) visual pathway, and their activation is consistent with the patient's report that blue light differentially evoked photophobia. This appears to be the first demonstration of functional activation of the ipRGC pathway during photophobia in a patient.
... Nonetheless, so far, there have been no major randomized control trials for photophobia management (Albilali and Dilli, 2018). The current treatment of this disorder actually remains a challenge for ophthalmologists and relies primarily on optical means such as wearing filtering glasses (Hoggan et al., 2016;Katz and Digre, 2016). Ubiquitous presence of artificial light sources highly emitting in blue spectrum complicates the situation additionally (Lupis, 2017;Text Request, 2017). ...
... This issue has been gaining more attention since the spectra of modern light sources contain an important blue part. Nonetheless, the correspondent underlying mechanisms are still debated (Digre and Brennan, 2012;Matynia and Gorin, 2013;Marshall, 2014;Katz and Digre, 2016;Lupis, 2017;Text Request, 2017;Wu and Hallett, 2017;Albilali and Dilli, 2018). Here, we investigated in vivo the origins and effects of spectrum-dependent photophobia by means of FIGURE 5 | Light-induced retinal inflammation (2). ...
Article
Full-text available
Photophobia may arise from various causes and frequently accompanies numerous ocular diseases. In modern highly illuminated world, complaints about greater photosensitivity to blue light increasingly appear. However, the pathophysiology of photophobia is still debated. In the present work, we investigated in vivo the role of various neural pathways potentially implicated in blue-light aversion. Moreover, we studied the light-induced neuroinflammatory processes on the ocular surface and in the trigeminal pathways. Adult male C57BL/6J mice were exposed either to blue (400-500 nm) or to yellow (530-710 nm) LED light (3 h, 6 mW/cm2). Photosensitivity was measured as the time spent in dark or illuminated parts of the cage. Pharmacological treatments were applied: topical instillation of atropine, pilocarpine or oxybuprocaine, intravitreal injection of lidocaine, norepinephrine or "blocker" of the visual photoreceptor transmission, and intraperitoneal injection of a melanopsin antagonist. Clinical evaluations (ocular surface state, corneal mechanical sensitivity and tear quantity) were performed directly after exposure to light and after 3 days of recovery in standard light conditions. Trigeminal ganglia (TGs), brainstems and retinas were dissected out and conditioned for analyses. Mice demonstrated strong aversion to blue but not to yellow light. The only drug that significantly decreased the blue-light aversion was the intraperitoneally injected melanopsin antagonist. After blue-light exposure, dry-eye-related inflammatory signs were observed, notably after 3 days of recovery. In the retina, we observed the increased immunoreactivity for GFAP, ATF3, and Iba1; these data were corroborated by RT-qPCR. Moreover, retinal visual and non-visual photopigments distribution was altered. In the trigeminal pathway, we detected the increased mRNA expression of cFOS and ATF3 as well as alterations in cytokines' levels. Thus, the wavelength-dependent light aversion was mainly mediated by melanopsin-containing cells, most likely in the retina. Other potential pathways of light reception were also discussed. The phototoxic message was transmitted to the trigeminal system, inducing both inflammation at the ocular surface and stress in the retina. Further investigations of retina-TG connections are needed.
... The ipRGCs have been proposed to cause deep ocular pain and photophobia, both of which are major symptoms of eye fatigue. Reduced activation of ipRGCs by blue-light shield shading could also be as effective at relieving eye fatigue as eye closure and darkness, via the photophobic association of ipRGCs [28][29][30]. ...
... Indeed, it is well known that many patients complain of eye fatigue while opening their eyes even without watching anything. This study did not show an association between photophobia and GCC thickness; however, photophobia is a multifactorial manifestation in human patients [28][29][30], and GCC alone might not be a contributing factor. ...
Article
Full-text available
Eye fatigue is a common health problem across all age groups. Herein, we explored the correlation between eye fatigue and thickness of the retinal nerve fiber layer (NFL). Included in the NFL are intrinsically photosensitive retinal ganglion cells (ipRGCs), which are associated with trigeminal pain. This retrospective cross-sectional study included outpatients with best-corrected visual acuity above 20/30 in both eyes and without dry eye, glaucoma, or retinal disease. A total of 1981 patients were initially enrolled and 377 patients were declared as eligible for the study analysis. We tested subjects for the presence of major ocular symptoms and measured thickness of ganglion cell complex (GCC) using optical coherence tomography. A total of 377 outpatients (46.4% men, mean age of 57.1 years) were enrolled for analysis, based on the interview-reported prevalence of six eye symptom, as follows: 31.5% for eye fatigue, 19.2% for blurring, 18.6% for dryness, 15.7% for photophobia, 13.5% for irritation, and 4.6% for pain. The macular GCC was significantly thicker in subjects with eye fatigue compared to the group not reporting eye fatigue (103.8 μ m versus 100.3 μ m, P = 0.014). Regression analysis identified eye fatigue ( P = 0.026, β =0.122, adjusted for age and sex) and dryness ( P =0.024, β =0.130) as significantly correlated with the macular GCC thickness, while the full macular thickness showed no significant correlation. In conclusions, eye fatigue and dryness were positively associated with thickness of the macular GCC. Nonvisual symptoms might therefore play a role in the development of eye fatigue.
... Os autores sugeriram que o filtro provavelmente facilitou a atividade cortical e diminuiu as distorções visuais. Estudos com tomografia e com ressonância magnética funcional corroboram esses achados, tendo observado uma redução da hiperexcitabilidade cortical com o uso da intervenção espectral (Chouinard, Zhou, Hrybouski, Kim, & Cummine, 2012, Denuelle, Boulloche, Payoux, Fabre, Trotter, & Géraud, 2011, Huang, Zong, Wilkins, Jenkins, Bozoki, & Cao, 2011, Katz, &Digre, 2016 e também a supressão dos sintomas clínicos em 90% dos pacientes portadores de enxaqueca induzida por estresse visual (Guimarães, 2010). ...
Chapter
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A leitura é uma habilidade cognitiva complexa, fundamental para o sucesso acadêmico e profissional na vida adulta. As dificuldades de leitura podem envolver alterações no processamento subcortical da informação visual não responsivas às abordagens pedagógicas habituais voltadas para problemas cognitivos de decodificação grafema–fonema, lexicais ou de processamento fonológico. Neste contexto a intervenção terapêutica deve ser direcionada para a identificação do tipo e intensidade dos distúrbios visuais a serem corrigidos, o que permite uma conduta eficaz e personalizada diante das demandas laborais, acadêmicas e sociais de cada caso (Guimarães & Guimarães, 2013). Os exames oftalmológicos de rotina se restringem a quantificar a capacidade de visualizar estímulos estáticos de alto contraste (letra preta no fundo branco), patologias orgânicas do globo ocular, alterações binoculares e alinhamento entre os olhos. Problemas refracionais, como a miopia e o astigmatismo, degradam a acuidade visual e consequentemente a eficiência leitora, sendo as alterações ópticas habitualmente corrigidas por meio de óculos de grau. No entanto, a leitura requer a integração com outro centro de processamento visual, indo, portanto, além das habilidades relacionadas à alta resolução espacial aferidas pelo exame da acuidade visual e que são processadas pelo sistema parvocelular. Assim, a leitura proficiente depende não só do sistema parvocelular, mas também da integridade do sistema magnocelular, considerado o caminho visual dominante na leitura de textos por atuar na mediação da capacidade de identificar de forma rápida e sequencial as letras e ainda controlar a orientação visual da atenção, das fixações e da sincronia binocular (Greatrex & Drasdo, 1995, Chase, Ashourzadeh, Kelly, Monfette, & Kinsey, 2003; Stein, 2003, 2018). Exemplificando, para se ler um livro de 200 páginas, o sistema magnocelular deve controlar ambos os olhos para que façam centenas de milhares de movimentos sacádicos curtos da esquerda para a direita, com fixações estáveis (pausas entre as sacadas) de 200 a 400 milissegundos para a extração da informação visual e com poucos movimentos de correção da direta para a esquerda (Regressões). Em tarefas de leitura, os déficits magnocelulares levam a instabilidade no controle da coordenação dos olhos e dificuldade na correta fusão da imagem pelo cérebro, provocando distorções visuais das palavras e do texto mesmo na ausência de problemas refracionais (Allen, Dedi, Kumar, Patel, Aloo, & Wilkins, 2012, Monger, Wilkins, & Allen, 2015, Solan, Ficarra, Brannan, & Rucker, 1998, Stein, 2001). O clássico estudo de Livingstone, Rosen, Drislane, e Galaburda (1991) demonstrou anormalidades post-mortem nas camadas magnocelulares dos núcleos geniculados laterais de disléxicos, mas não nas camadas parvocelulares, quando comparados a um grupo controle de leitores típicos. Diferentes estudos corroboraram o achado de que disléxicos possuem menores respostas a estímulos rápidos e de baixo contraste (coerentes com déficits no sistema magnocelular), mantendo respostas normais a estímulos lentos ou de alto contraste (preservação do sistema parvocelular) (Gori, Seitz, Ronconi, Franceschini, & Facoetti, 2015, Pammer, & Wheatley, 2001). Leituras mais longas, excedendo a dez minutos, tendem a apresentar uma instabilidade progressiva na movimentação ocular, gerando uma dificuldade no processamento visual, com perda da qualidade e consequente estresse visual. Os principais sintomas do estresse visual são distorções visuoperceptuais, fotosensibilidade, irritabilidade e agitação sob luz fluorescente e ainda défice na percepção de profundidade (Guimarães, Vilhena, & Guimarães, 2017, Loew, & Watson, 2012, 2013). As distorções mais frequentemente reportadas são sombras e halos ao redor das palavras, espaçamentos irregulares em meio ao texto, e percepção de letras se movendo, vibrando ou se destacando do papel (Evans, Allen, & Wilkins, 2017, Stein, & Walsh, 1997). Os esforços para compensar essas dificuldades levam a queixas de cansaço visual progressivo, dor nos olhos, lacrimejamento, piscar excessivo, cefaleia ou enxaquecas (Kriss, & Evans, 2005, Scott et al., 2002). O estresse visual prejudica ainda a manutenção da atenção, a aprendizagem em sala de aula e inflige desgastes emocionais e ocupacionais, comprometendo o interesse e o apreço pela leitura. A intervenção terapêutica feita pela prescrição de lentes ópticas, com ou sem grau refracional, acrescidas de filtros para bloqueio específico e individual das faixas espectrais hipersensibilizantes regulariza a velocidade de transmissão do sistema magnocelular, reequilibrando a sua relação com o sistema parvocelular (Breitmeyer, & Williams, 1990, Croyle, 1998, Solan, Ficarra, Brannan, & Rucker, 1998, Ray, Fowler, & Stein, 2005, Guimarães, Vilhena, Pinheiro, & Guimarães, 2018). Estima-se que 13% das crianças no ensino fundamental apresentem melhoras significativas da taxa de leitura com o uso de lâminas espectrais (Garcia, Momensohn-Santos, & Vilhena, 2017). Os efeitos do tratamento com Filtros Espectrais nos casos de disfunções oculomotoras, fotofobia e cansaço visual em déficits de leitura podem ser analisados via rastreadores oculares (eye-trackers) (Vilhena, Freitas, Guimarães, & Pinheiro, 2018). Os movimentos oculares refletem os processos cognitivos relacionados à percepção visuoespacial, à análise semântica do texto e ao processamento de informações. Razuk, Perrin-Fievez, Gerard, Peyre, Barela, & Bucci (2018) verificaram que crianças disléxicas leram mais rápido e com menor duração da fixação ocular com o uso de um Filtro Espectral Verde. Os autores sugeriram que o filtro provavelmente facilitou a atividade cortical e diminuiu as distorções visuais. Estudos com tomografia e com ressonância magnética funcional corroboram esses achados, tendo observado uma redução da hiperexcitabilidade cortical com o uso da intervenção espectral (Chouinard, Zhou, Hrybouski, Kim, & Cummine, 2012, Denuelle, Boulloche, Payoux, Fabre, Trotter, & Géraud, 2011, Huang, Zong, Wilkins, Jenkins, Bozoki, & Cao, 2011, Katz, &Digre, 2016) e também a supressão dos sintomas clínicos em 90% dos pacientes portadores de enxaqueca induzida por estresse visual (Guimarães, 2010). A mensuração da leitura de adultos é um desafio psicométrico, uma vez que o efeito de teto em testes de leitura é presente inclusive na avaliação de crianças (Pinheiro, Vilhena, & Cunha, 2017). Rastreadores oculares são instrumentos valorizados nas Clínicas de Neurociências da Visão (Neurovisão) e nos consultórios neuropsicopedagógicos, pois fornecem parâmetros objetivos dos movimentos oculares envolvida na leitura de textos, que são primariamente subcorticais e involuntários. Este estudo, de delineamento longitudinal, investigou o efeito terapêutico de uma ampla gama de Filtros Espectrais, considerando os diferentes parâmetros envolvidos na movimentação ocular e habilidade de leitura. Métodos Participantes O Comitê de Ética em Pesquisa da Universidade Federal de Minas Gerais aprovou todos os procedimentos do estudo [Aprovação nº 49765115.0.0000.5149], o qual foi conduzido em total conformidade com o Código de Ética da World Medical Association (Declaração de Helsinki, 2008) para pesquisa envolvendo seres humanos. Foram selecionados retrospectivamente todos os 177 pacientes adultos atendidos entre 01/2013 a 02/2016, no Departamento de Neurovisão do Hospital de Olhos de Minas Gerais – Clínica Dr. Ricardo Guimarães. Os pacientes possuíam de 18 a 59 anos, com média de 30.6 anos (Desvio Padrão de 11.0), sendo 50% homens. Instrumentos Foi utilizado o Visagraph III Eye-Movement Recording System (Taylor Associates, New York) para a análise dos movimentos oculares durante a leitura de textos. Este rastreador ocular (eye-tracker) é composto por um par de óculos sem lentes, no qual está acoplado um sistema de captação por sensores infravermelhos, conectado a um software de análise de dados. Com exceção da variável Compreensão de Texto (habilidade de alta ordem), os parâmetros listados na Tabela 1 possuem controle primariamente subcortical e involuntário. Para eliminar a discrepância binocular, a média de ambos os olhos foi calculada para as variáveis Fixações, Regressões, Alcance Perceptual e Duração da Fixações, uma vez que as correlações bivariadas de Pearson foram acima de 0.97. Os Filtros Espectrais usados nos testes haviam sido prescritos para uso em tempo integral, incluindo em atividades que requeriam intensa atividade visual (por exemplo, leitura prolongada de textos). Cada participante havia sido submetido previamente a um protocolo detalhado envolvendo exames psicofísicos, clínicos e o diagnóstico específico do(s) tipo(s) de filtros(s) necessário(s) para o bloqueio completo das faixas de luz visível ou faixas espectrais hipersensibilizantes. A seleção dos filtros é feita por meio da exposição do paciente a estímulos estressores ao sistema visual, com subsequente análise do grau de alívio/supressão da maioria dos sintomas visuais objetivos e subjetivos, como por exemplo, o maior conforto obtido sob o uso do filtro ideal. Dado o número de filtros e combinações possíveis, há centenas de opções possibilitando alto grau de especificidade na seleção individual. Na amostra do presente estudo, foram selecionados de forma individual ou composta, 49 diferentes Filtros Espectrais. Procedimentos Todos os pacientes foram submetidos a um protocolo oftalmológico para adequada prescrição da correção refracional e, caso necessário, houve encaminhamento e tratamento visual prévio à seleção de Filtros Espectrais. O protocolo incluiu a análise da acuidade visual monocular e binocular para longe e para perto, pesquisa de aberrações de baixa e alta ordem, exame ortóptico, aferição da dominância ocular e estereopsia, e avaliação da visão de cores (Teste de Placas de Ishihara Pseudo-Isocromáticas 25 e Teste de Tonalidades D-15 Farnsworth-Munsell simples e desaturado), da sensibilidade ao contraste e do campo visual periférico dinâmico. Para a análise do padrão dos movimentos oculares, os sensores do rastreador ocular foram alinhados à borda externa da pupila de cada indivíduo. A primeira e as duas últimas linhas do texto foram desconsideradas automaticamente pelo software do Visagraph III™ com o objetivo de representar de maneira fidedigna o padrão oculomotor de leitura. O material de leitura consistia em um único parágrafo de texto em tinta preta, impresso em papel branco, em fonte Times New Roman, tamanho 18. Os textos foram lidos em voz alta, com uma distância de visualização de 40 a 45 cm, sob iluminação de escritório padrão (duas lâmpadas de teto fluorescentes branca fria, tubos de 60 cm de 20W, temperatura de cor correlacionada de 5.000K e ciclo de intermitência de 120 Hz). Após cada leitura, os participantes responderam dez questões fechadas sobre o conteúdo do texto recém lido. O padrão oculomotor de leitura (linha de base) foi analisado na primeira consulta, sendo considerado como condição pré-teste, sem o uso de filtros. A consulta de retorno foi considerada como pós-teste, condição onde o Filtro Espectral fora usado de forma continuada e em tempo integral. A média de tempo entre o pré-teste e o pós-teste foi de 18 meses. Análise estatística O IBM SPSS Statistics (versão 21.0, Chicago, Illinois, EUA) foi utilizado para todas as análises de dados. Para examinar os efeitos da intervenção com Filtros Espectrais nos movimentos oculares foi conduzida uma série de ANOVA oneway, com F ajustado de acordo com o método de Greenhouse-Geisser. Para estabelecer a significância clínica das diferenças, o d de Cohen foi calculado para determinar o tamanho do efeito e foi interpretado usando os critérios de Cohen (1988) de 0.2 para um efeito pequeno, 0.5 para um efeito médio e 0.8 para um efeito grande. O valor de p inferior a 0.05 foi considerado estatisticamente significativo. RESULTADOS Após o tratamento com o uso de Filtros Espectrais (média de 18 meses entre condições), os participantes apresentaram uma redução moderada (d = 0.57, 0.54 e 0.49) e significativa (p < 0.0001) de -33% no número de Fixações oculares, de -46% no número de Regressões e de -18% na dificuldade da Direção Correta Esquerda–Direita, quando comparados com a linha de base (ver Tabela 2 e Figura 1). Houve um aumento moderado (d = 0.50 a 0.68) e significativo (p < 0.001) de 43% no Alcance Perceptual, de 29% no número de palavras lidas por minuto e de 11% na Compreensão de Texto. A Eficiência Relativa da leitura apresentou um forte aumento de 79% após o tratamento (d = 1.09, p < 0.001). Houve uma melhora, com efeito pequeno (d = 0.30) e significativo (p = 0.0008), de 7% na Correlação Binocular. A Duração da Fixação não apresentou diferença significativa entre testagens (p = 0.48). Discussão O tratamento com Filtros Espectrais produziu um efeito moderado na melhora da atividade oculomotora na leitura de adultos. Após a intervenção (pós-teste) registrou-se um menor número de Fixações e de Regressões oculares em paralelo a uma maior correlação binocular, o que evidencia maior facilidade na focalização do mesmo número de palavras. O maior alcance perceptual proporciona uma melhor capacidade cognitiva para armazenar e manipular a informação, habilidade fundamental na decodificação automática das palavras. Essa capacidade permitiu um aumento de 29% na velocidade de leitura, com 58 palavras lidas a mais por minuto. Os resultados mostram que o bloqueio espectral seletivo pode aprimorar a extração da informação visual com o aumento da eficiência, fluência e compreensão leitora. Esses achados sugerem uma melhor redistribuição da ativação cortical, como encontrado em outros estudos (Chouinard, Zhou, Hrybouski, Kim, & Cummine, 2012, Denuelle, Boulloche, Payoux, Fabre, Trotter, & Géraud, 2011). Soares e Gontijo (2016) publicaram uma revisão da literatura, composta por 16 trabalhos, na qual foi evidenciado que há uma base bioquímica, genética e imunológica envolvida nos pacientes que apresentam estresse visual. Estudos assinalaram quem há uma diferença na proporção de lipídios no sangue (p < 0.05; d > 0.08; menor colesterol total e mais ácido heptadecanoicono plasma) e de aminoácidos e ácidos orgânicos na urina (p < 0.05; d > 0.05), sinalizando um metabolismo anormal associado a alterações de natureza sistêmica e imunológica. A revisão sistemática de Evans e Allen (2016) mostraram que a intervenção com Filtros Espectrais, além de ser segura e não invasiva, alivia os sintomas de astenopia e melhora o desempenho de leitura dos pacientes com estresse visual. Estes mesmos autores ressaltaram a importância do diagnóstico diferencial entre os casos de estresse visual com aqueles envolvendo erros refrativos, heteroforia descompensada e déficits na amplitude de acomodação, por serem também indutores de astenopia e/ou intensificadores dos sintomas de estresse visual. Em um artigo com quatro experimentos, Gori, Seitz, Ronconi, Franceschini, & Facoetti (2015) verificaram: 1) a presença de dificuldade na percepção de movimento em disléxicos quando comparados a dois grupos controles; 2) que a percepção de movimento visual de crianças na fase de pré-leitura prediz o desenvolvimento leitor; e que 3) os treinamentos no sistema magnocelular visual levam a uma melhor habilidade de leitura em crianças e adultos com dislexia do desenvolvimento. Gori, Seitz, Ronconi, Franceschini, & Facoetti concluíram que há de fato uma relação causal entre déficit no sistema magnocelular e a dislexia, fechando um debate de 30 anos. Flint e Pammer (2018) verificaram, em um estudo com dois experimentos, que adultos analfabetos obtiveram o mesmo desempenho do que os leitores normais e semianalfabetos em tarefas temporais e espaciais específicas do sistema magnocelular visual, tendo todos os três grupos um desempenho melhor do que o grupo de leitores disléxicos. O desempenho inferior dos disléxicos ocorreu tanto no experimento 1 com um teste de coerência do movimento (F(3, 79) = 104.9, p < 0.0001, d = 0.81), quanto no experimento 2 com o teste Frequency-doubling Illusion (F(3, 79) = 283.8, p< 0.005, d = 0.86). Os autores concluem que essa falha funcional da via visual dorsal na dislexia provavelmente não é consequência da falta de leitura, responsabilizando como causa o processamento magnocelular. Utilizando de analogia no título do artigo, Flint e Pammer consideram que o ovo veio primeiro que a galinha, assim, o déficit magnocelular veio primeiro que a dislexia. O presente estudo acompanhou 177 adultos que fizeram tratamento com uma ampla variedade de Filtros Espectrais, prescritos individualmente. Por meio de parâmetros objetivos de rastreamento ocular, foi demonstrado que houve uma melhora da eficiência dos movimentos oculares e da habilidade de leitura, com elevada significância estatística e moderado efeito clínico. A oculomotricidade está sob controle cortical e subcortical e responde a mecanismos de controle inibitórios que controlam o tempo de fixação, o alcance sacádico e a cognição e que afetam também a coordenação oculomotora binocular fina quando se percorre uma linha de texto. As lentes espectrais suprimiram ou reduziram as três principais queixas visuais dos pacientes: a sensibilidade à luz que limita a legibilidade, o conforto e a duração máxima da leitura, as disfunções oculomotoras que afetam a coordenação binocular fina quando se percorre uma linha de texto; e a disfunção acomodativa que altera a clareza textual. Houve, também, o reajuste da composição espectral e redução da luminância pela alteração do locus do feixe luminoso na retina e redução da intensidade da luz associada ao bloqueio seletivo dos comprimentos de onda hipersensibilizantes (Willeford, Fimreite, Ciuffreda, 2016). Conclusão Pacientes adultos, após o tratamento com Filtros Espectrais, apresentaram uma melhora significativa da habilidade de leitura e dos parâmetros oculomotores envolvidos no rastreamento visual do texto, quando comparados com a linha de base. Foi verificada uma forte melhora do parâmetro Eficiência Relativa da leitura. A redução no número de fixações oculares permite a estabilidade da imagem na região foveal. A redução no número de Regressões melhorou a fluência de leitura, o que reduz a dificuldade dos movimentos sacádicos na direção esquerda–direita. A melhora dos parâmetros oculomotores com o uso de Filtros Espectrais favoreceu a capacidade cognitiva e o armazenamento e manipulação da informação, culminando com a melhor compreensão do texto. Filtros Espectrais são uma intervenção oftalmológica não-invasiva e não-medicamentosa que melhoraram a eficiência de leitura em adultos com fotofobia, dificuldades de leitura, cansaço visual e sobrecarga sensorial podendo ser usados acrescidos a lentes ópticas com e sem correção refracional.
... Mild TBI is the most common classification (70-90 per cent of cases), comprising patients who experience brief (less than 30 minutes) or no loss of consciousness at the time of injury, exhibit no post-traumatic amnesia and lose minimal motor or verbal function. 9,10 Despite the lack of clinically detectable inflammation within the eye and the maintenance of good visual acuity, 11 the post-traumatic ocular symptoms of mild TBI can be debilitating. Accommodative dysfunction, oculomotor deficits, reading difficulties and visual field defects are all associated with mild TBI. ...
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Background Photophobia is a common sequela of traumatic brain injury (TBI). Diagnostic tools for this debilitating condition are lacking. This investigation sought to determine whether masked observers can distinguish subjects with TBI‐associated photophobia from matched controls based on video recordings of their ocular responses to light stimulation. Methods Cohorts of students (n = 20), photophobic TBI subjects (n = 28) and their matched control subjects (n = 12) were recruited. A custom pupillometer delivered bright (10¹³–10¹⁴ photons/s/cm²), flashing (0.10 Hz) red (625 nm) and blue (470 nm) light stimuli to subjects, and consensual pupil light responses were recorded. Using a five‐point scale, masked observers later graded light aversion behaviour in the pupil video recordings obtained from the student cohort based on observed blinking, tearing and squinting. A grading scale was developed and used by masked observers to grade light aversion behaviour in videos obtained from subjects with post‐TBI photophobia and the matched controls. These subjects also scored their perceived discomfort during each light pulse using a five‐point scale. Results The subjects in the TBI cohort scored both the blue and red flashing stimuli as evoking more discomfort, relative to control subjects, consistent with their reported photophobia. There was strong agreement among the masked observers for their grades of light aversion behaviour in the videos of ocular light stimulation (interclass correlation co‐efficient = 0.78; 29 per cent perfect concordance). However, the median grades for the videos obtained from the TBI subject cohort were not significantly different from those for the control group. Conclusions Clinicians cannot diagnose TBI‐related photophobia based solely on video recordings of ocular responses to light. The need remains for an objective test to diagnose and manage this prevalent post‐TBI symptom.
... It is a subjective symptom associated with several ophthalmic and neurological conditions. [9] Visual photosensitivity causes discomfort when the eyes are exposed to natural or artificial light sources outdoors or indoors. Glare, involuntary blinking, squeezing of eyelids, and watering in bright light or bright colors can be the symptoms associated with visual photosensitivity. ...
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Primary objective: Visual photosensitivity following mild traumatic brain injury (mTBI) can cause mild discomfort to significant pain and can affect a person's ability to lead a regular life and perform normal activities. The purpose of the present study is twofold: (1) To determine the recovery pattern of visual photosensitivity following mTBI and (2) to find out whether the onset of visual photosensitivity and its recovery pattern is any different among habitual screen users (HSU) (chronic exposure to digital device screens). Materials and methods: This study was a hospital-based prospective, analytical, observational study. The study period was from July 2017 to March 2019. All the mTBI patients with visual photosensitivity who fulfilled the inclusion Criteria were followed up for 1 year to capture their recovery profile. Results: In 60% of the patients, the time of appearance of visual photosensitivity was at around 3 month's post-mTBI. Nearly 66.6% of patients suffering from visual photosensitivity following mTBI recovered within 3 months following the onset of their symptoms. The symptoms of visual photosensitivity appeared earlier among the HSU as compared to nonscreen users (P = 0.0039). The recovery from the symptoms of visual photosensitivity following mTBI is delayed in HSU (P = 0.0028). The patients in whom the symptoms of visual photosensitivity persisted beyond a year were predominantly HSU (P = 0.0062). Conclusions: The present study has given a new insight on the timeline of recovery for the patients with visual photosensitivity following mTBI. To the best of our knowledge, this is the only study which has shown how chronic exposure to blue light from digital device screens can affect the recovery of visual symptoms such as visual photosensitivity following mTBI.
... S-cones are potentially evoked at the peak of 430 nm (nm) light 14 . The action spectrum of iRGCs and rods peak at 480 nm 15 and 500-510 nm 16 , respectively. ...
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Inherited retinal dystrophy (IRD) patients often experience photophobia. However, its mechanism has not been elucidated. This study aimed to investigate the main wavelength of light causing photophobia in IRD and difference among patients with different phenotypes. Forty-seven retinitis pigmentosa (RP) and 22 cone-rod dystrophy (CRD) patients were prospectively recruited. We designed two tinted glasses: short wavelength filtering (SWF) glasses and middle wavelength filtering (MWF) glasses. We classified photophobia into three types: (A) white out, (B) bright glare, and (C) ocular pain. Patients were asked to assign scores between one (not at all) and five (totally applicable) for each symptom with and without glasses. In patients with RP, photophobia was better relieved with SWF glasses {"white out" (p < 0.01) and "ocular pain" (p = 0.013)}. In CRD patients, there was no significant difference in the improvement wearing two glasses (p = 0.247-1.0). All RP patients who preferred MWF glasses had Bull's eye maculopathy. Meanwhile, only 15% of patients who preferred SWF glasses had the finding (p < 0.001). Photophobia is primarily caused by short wavelength light in many patients with IRD. However, the wavelength responsible for photophobia vary depending on the disease and probably vary according to the pathological condition.
... Photophobia is a common and debilitating sensory disturbance characterized by light-induced ocular or cranial discomfort that can be accompanied by a subsequent increase in tear production and squinting responses [1,2]. The most common neurologic condition associated with photophobia is migraine, with 80%-90% of patients experiencing photophobia [3,4] both during (ictally) and in between (inter-ictally) migraine attacks [5][6][7]. ...
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The purpose of this pilot study was to investigate the light-induced pupillary and lacrimation responses mediated by intrinsically photosensitive retinal ganglion cells (ipRGCs) in migraine. Ten participants with episodic migraine and normal tear production, as well as eleven visually normal controls participated in this study. Following an initial baseline trial (no light flash), participants received seven incremental and alternating red and blue light flashes. Pupillometry recording of the left eye and a 1-min anesthetized Schirmer's test of the right eye (using 0.5% proparacaine) were performed simultaneously. Intrinsic and extrin-sic ipRGC photoactivities did not differ between migraine participants and controls across all intensities and wavelengths. Migraine participants, however, had significantly lower lacrima-tion than controls following the highest blue intensity. A positive correlation was found between melanopsin-driven post-illumination pupillary responses and lacrimation following blue stimulation in both groups. Our results show that participants with self-reported photo-phobia have normal ipRGC-driven responses, suggesting that photophobia and pupillary function may be mediated by distinct ipRGC circuits. The positive correlation between mela-nopsin-driven pupillary responses and light-induced lacrimation suggests the afferent arm of the light-induced lacrimation reflex is melanopsin-mediated and functions normally in migraine. Lastly, the reduced melanopsin-mediated lacrimation at the highest stimulus suggests the efferent arm of the lacrimation reflex is attenuated under certain conditions, which may be a harbinger of dry eye in migraine.
... Photophobia has been associated with different conditions. 39 In 2019, Ueno et al studied photophobia through electroretinography in patients with paraneoplastic retinopathy; they found a relation between autoantibody transient receptor potential cation channel, subfamily M, member 1 (Anti-TRPM1), and photophobia. 40 Due to the limited number of studies reporting this association, we present the first study describing a statistically significant association between inflammatory biomarkers with photophobia. ...
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Purpose: Ocular involvement is frequent in autoimmune diseases and even can be the first manifestation. There are multiple descriptions in the literature around the world regarding this topic. However, we evidenced a lack of studies analyzing the relationship between the ocular manifestations and systemic biomarkers, especially in Latinamerica. Therefore, this study aimed to examine the relationship between the positivity of inflammatory biomarkers and the ocular manifestations in a Colombian cohort of rheumatological patients. Patients and methods: We conducted an observational, descriptive, non-comparative cross-sectional study in a rheumatology center, in Bogotá, Colombia, from 2013 to 2019. We calculated a sample size of 797 patients to assess the prevalence of ocular manifestations and inflammatory biomarkers. We performed univariate analyses for categorical and continuous variables and bivariate analyses using the Chi-square and Fisher's exact test for categorical variables. Results: Women represented 84% of the population, and the mean age was 54.61± 15.64 years. Of 797 patients, 21.45% reported one or more ophthalmological diagnoses, being keratoconjunctivitis sicca (KCS) the most common (15.93%), followed by uveitis, and cataract (1.38%, each one). Regarding ophthalmological symptoms, 35% presented at least one, being dry eye sensation (DE) the most common (30.86%), followed by ocular pain (2.76%), red eye, and decreased visual acuity (2.63%, each one). The antibodies or inflammatory biomarkers most frequently found were antinuclear antibodies (ANAs) (35.3%), C-reactive protein (28.7%), and rheumatoid factor (27.9%). We found statistical associations between consumption of complement 3, anti-CCP, anti-RO, and anti-LA antibodies with ocular manifestations such as photophobia, DE, conjunctivitis, KCS, uveitis, retinal vasculitis, and maculopathy. Conclusion: Ocular manifestations are frequently found in patients with positive antibodies and inflammatory biomarkers. Our results suggest antibodies and inflammatory molecules could be biomarkers for ocular manifestations in patients with rheumatological diseases. This study provides the basis for future longitudinal studies.
... Since artificial sources and particularly digital screens highly emit in the blue spectrum, the issue of blue light noxiousness has been much discussed [2,3]. In western countries, one of the main reason for visiting an ophthalmologist is exacerbated photosensitivity and ocular symptoms of discomfort in various luminous conditions [4][5][6][7] like being in front of monitors [8][9][10][11]. So far a lot of studies have already investigated the UV and blue-light photodamage related to ocular diseases such as keratitis, cataract, and retinal degeneration [12][13][14][15][16]. Similarly, the interest in dry-eye-related phototoxicity on the ocular surface is constantly growing [17][18][19][20][21][22]. ...
Article
Today the noxiousness of blue light from natural and particularly artificial (fluorescent tubes, LED panels, visual displays) sources is actively discussed in the context of various ocular diseases. Many of them have an important neurologic component and are associated with ocular pain. This neuropathic signal is provided by nociceptive neurons from trigeminal ganglia. However, the phototoxicity of blue light on trigeminal neurons has not been explored so far. The aim of the present in vitro study was to investigate the cytotoxic impact of various wavebands of visible light (410–630 nm) on primary cell culture of mouse trigeminal neural and glial cells. Three-hour exposure to narrow wavebands of blue light centered at 410, 440 and 480 nm of average 1.1 mW/cm² irradiance provoked cell death, altered cell morphology and induced oxidative stress and inflammation. These effects were not observed for other tested visible wavebands. We observed that neurons and glial cells processed the light signal in different manner, in terms of resulting superoxide and hydrogen peroxide generation, inflammatory biomarkers expression and phototoxic mitochondrial damage. We analyzed the pathways of photic signal reception, and we proposed that, in trigeminal cells, in addition to widely known mitochondria-mediated light absorption, light could be received by means of non-visual opsins, melanopsin (opn4) and neuropsin (opn5). We also investigated the mechanisms underlying the observed phototoxicity, further suggesting an important role of the endoplasmic reticulum in neuronal transmission of blue-light-toxic message. Taken together, our results give some insight into circuit of tangled pain and photosensitivity frequently observed in patients consulting for these ocular symptoms.
... p=0.01) [92]. Tinted lens spectacles that block out specific wavelengths of light (~480 nm) are also helpful in managing individuals with photophobia [93], including those with comorbid migraine [94]. ...
Article
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Purpose of Review Confocal microscopy and aethesiometry have allowed clinicians to assess the structural and functional integrity of corneal nerves in health and disease. This review summarizes literature on nerves in dry eye disease (DED) and discusses how this data can be applied to DED diagnosis and treatment. Recent Findings Subjects with DED have a heterogeneous symptom and sign profile along with variability in nerve structure and function. Most studies have reported lower nerve density and sensitivity in aqueous tear deficiency, while findings are more inconsistent for other DED subtypes. Examining nerve status, along with profiling symptoms and signs of disease, can help categorize subjects into disease phenotypes (structural and functional patterns) that exist under the umbrella of DED. This, in turn, can guide therapeutic decision-making. Summary Due to the heterogeneity in symptoms and signs of DED, corneal nerve evaluations can be valuable for categorizing individuals into disease sub-types and for guiding clinical decision-making.
... Treatment of photophobia often involves polarized lenses, tinted lenses, filters, or visors [48] in addition to migraine treatment (when present). FL-41 tinted lenses have specifically been studied and demonstrated reduction in patient sensitivity to light [49]. Currently a computerized rehabilitation program has shown promise in improving a variety of ocular motor deficits in the setting of mTBI; however, these results are pending a randomized controlled trial [50]. ...
Article
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Purpose of Review Mild traumatic brain injury, or concussion, is a major cause of disability. Vestibular and visual dysfunction following concussion is common and can negatively affect patients’ well-being and prolong recovery. Etiologies of visual and vestibular symptoms are numerous, including ocular, neuro-ophthalmic, otologic, and neuro-vestibular conditions. Some etiologies are benign and may be treatable, while others are potentially vision or life-threatening, making a focused history and examination essential. This review offers an approach to the evaluation and treatment of the most common neuro-visual and vestibular impairments that may result from concussion. Recent Findings Treatment of concussion including exercise, computerized programs, transcranial magnetic stimulation, gene therapy, stem cell therapy, and nanoparticles has shown promise. Summary Many novel therapies are in the pipework for visual and vestibular recovery after concussion; however, the treatment mainstay remains therapy and evaluation for co-existing diseases.
... Several peripheral sensors in the anterior of the eye contain melanopsin, a photopigment that offers a light transduction mechanism that may lead to pain perception. With a peak wavelength sensitivity of 480 nm, melanopsin-based photoreception can occur in intrinsically photosensitive retinal ganglion cells (ipRGCs) and is increasingly implicated as a source for light-induced pain (28)(29)(30)(31)(32). These ipRGCs can generate their own signal independent of rod and cone involvement in response to light absorption yet can additionally receive or relay input from classical RGCs and support cells (33)(34)(35)(36). ...
Article
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Supraspinal mechanisms of pain are increasingly understood to underlie neuropathic ocular conditions previously thought to be exclusively peripheral in nature. Isolating individual causes of centralized chronic conditions and differentiating them is critical to understanding the mechanisms underlying neuropathic eye pain and ultimately its treatment. Though few functional imaging studies have focused on the eye as an end-organ for the transduction of noxious stimuli, the brain networks related to pain processing have been extensively studied with functional neuroimaging over the past 20 years. This article will review the supraspinal mechanisms that underlie pain as they relate to the eye.
... • Patients with cone and rod dystrophies have intense photophobia and dyschromatopsia -affecting their day to day activities. [1][2][3][4]9 • Tinted glasses and filters -Management of photophobia. [5][6][7][8] • No recent advancements are available to stop the progression. ...
Poster
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This poster explains a study on prescribing patterns of low vision devices in patients with cone dystrophy, cone rod dystrophy and rod cone dystrophy.
... Photic blink reflex can function as an accessory pupil, further controlling retinal luminance in addition to pupil size [11]. Since this reflex has a shorter latency than the pupil light reflex, it may play a more significant role in modulating retinal luminance under both a light stimulus and a steady-state light [11,12]. Even though the TEC is such a common feature in IXT, little is known about the association between TEC and IXT, and, thus, we should explore the phenomenon more thoroughly. ...
Article
Full-text available
Background: This study aimed to present a simple method for evaluating transient eye closure (TEC) evoked by bright light and find the agreement between TEC and photosensitivity. We also assessed the associated factors with TEC in the patients with intermittent exotropia (IXT). Methods: In this retrospective study, IXT patients were exposed to different brightness: darkness, low-intensity white light, and high-intensity white light using a near-infrared camera vision monitor system (Mon CV3, Metrovision, France). TEC was considered to be present if the subject closed his or her eyes immediately, and for more than half of the scotopic lid fissure distance in response to the high-intensity or low-intensity photopic stimulus of light, compared with lid fissure distance in the scotopic phase. We assessed the presence of photosensitivity using a questionnaire and evaluated the agreement between TEC and photosensitivity. We also investigated the sensory fusion, motor fusion, and pupil dynamic components for the existence of TEC in IXT patients. Results: Sixty-one patients with IXT were included. With the new method to evaluate TEC under different light intensities, 27 (44.3%) of the 61 IXT patients showed TEC, and 34 (55.7%) did not demonstrate TEC. TEC under high-intensity white light had a strong correlation with self-reporting photosensitivity (r = 0.77). The smaller angle of deviation at near was associated with the presence of TEC, with statistical significance (p = 0.04). Normal sensory status at a distance was significantly associated with TEC (p < 0.01). Multivariate analysis using multiple logistic regression analysis showed that normal sensory status was significantly associated with TEC (p = 0.02). Conclusions: The test using a near-infrared camera vision monitor system was a simple and objective tool in identifying TEC evoked by bright light. The presence of TEC strongly correlated with self-reporting photosensitivity in patients with IXT. However, TEC may be an independent phenomenon with motor alignment, stereopsis, and pupil reflex pathway in patients with IXT.
... Aniridia is known to cause photophobia and glare due to the absence of the iris protection. [6,16] In conclusion, we report the case of a traumatic total iridectomy due to iris extrusion through a 2.75 mm cataract incision after blunt trauma, with the distinct feature of an intact IOL and capsular bag, plus peripheral remnants of cortical material in the capsular bag and anterior capsule opacity that resemble a "pseudoiris" in a dilated pupil. There have been previous publications of traumatic expulsive iridodialysis with sparing of the IOL and capsular bag, but, to the best of our knowledge, our case seems to be the first to report a "pseudoiris". ...
Article
Blunt trauma may cause a wound in the site of the cataract incision in patients that have received this surgery, even decades after the procedure. The opening of the incision seems to avoid globe rupture, acting as a "liberating valve" We report a case of a 92-year-old woman with advanced dry macular degeneration who is referred to our department after suffering a blunt trauma in her left eye with a nightstand. She was diagnosed of a traumatic total iridectomy due to iris extrusion through a 2.75 mm cataract incision after injury and vitreous hemorrhage, sparing an intact intraocular lens and capsular bag, as well as peripheral remnants of cortical material in the capsular bag and anterior capsule opacity resembling "pseudoiris". After the vitreous hemorrhage was completely resolved she referred no photophobia. Consequently, although a bad visual acuity of the patient could mitigate patient's photophobia, we believed that her "pseudoiris" plays an important role in diminishing the possible symptoms of photophobia.
... Психогенный БФС считается относительно редким состоянием. В серии наблюдений пациентов с психогенными расстройствами движения (n=131) БФС или другие гиперкинезы лица составляли только 0,3% [45]. Среди прочих конверсионных гиперкинезов психогенный БФС встречался у 2-7% пациентов [46]. ...
Article
Blepharospasm (BPS) is a variant of focal dystonia manifested by involuntary eyelid spasms with eye closure and/or increased spontaneous blinking. Along with motor symptoms, this condition is characterized by sensory, affective, and cognitive disorders. Patients with BPS are found to have changes in the basal ganglia, cerebellum, primary/secondary sensorimotor and visual areas according to functional magnetic resonance imaging. This may reflect the involvement of above regions in suppressing defective movement and sensorimotor disintegration. Botulinum toxin therapy is the most effective treatment for BPS. The advantage of Xeomin® that does not contain complexing proteins, is characterized by a low probability of antibody production, is the ability to vary between-injection intervals. Probably, botulinum toxin therapy has a pathogenetic and modifying impact on BPS.
Article
Background: Although patients with abnormal light sensitivity may present to an ophthalmologist or optometrist for the evaluation of photophobia, there are no previous reviews of the most common causes of this symptom. Methods: We conducted a retrospective chart review of patients who presented to our eye center between 2001 and 2009 primarily for the evaluation of photophobia. We recorded demographics, ocular examination findings, and diagnoses of these patients. Results: Our population included 58 women and 53 men. The mean age at presentation to the clinic was 37 years (range 6 months-94 years). The most frequent cause of photophobia was migraine headache (53.7%), followed by dry eye syndrome (36.1), ocular trauma (8.2%), progressive supranuclear palsy (6.8%), and traumatic brain injury (4.1%). A significant proportion of patients (25.9%) left the clinic without a cause for their photophobia documented by the examining physician (11.7% of adults and 69.4% of children). Conclusions: Photophobia affects patients of all ages, and many patients are left without a specific diagnosis, indicating a significant knowledge gap among ophthalmologists and optometrists evaluating these patients.
Article
Background: Vestibular migraine (VM) is the most common neurologic cause of vertigo in adults and results in significant utilization of health care resources, but remains under-recognized and underdiagnosed. Evidence acquisition: Review of literature in PubMed using the following terms: vestibular migraine, migraine-associated vertigo, vertiginous migraine, benign recurrent vertigo, migraine-associated dizziness, migraine, migraine treatment, Meniere disease (MD), vertebrobasilar ischemia (VBI), posterior circulation stroke, benign paroxysmal positional vertigo, and episodic-ataxia Type 2 (EA2). Results: VM can manifest with a variety of vestibular symptoms, including spontaneous vertigo, triggered vertigo, positional vertigo, and head-motion dizziness. Patients may report more than 1 vestibular symptom. Episodes of vertigo are often, but not always, accompanied by headache. Auditory symptoms are frequently associated with VM attacks and may mimic the manifestations of MD. Other migrainous features that accompany VM attacks include photophobia, phonophobia, osmophobia, and visual aura. Interictally, patients may suffer from persistent dizziness or isolated paroxysmal vestibular symptoms. Mood disorders (particularly anxiety) are often found in VM. Abnormal neuro-otologic findings are not uncommon in patients with VM. Differential diagnoses for VM include MD, VBI, EA2, and migraine with brainstem aura. For rescue treatment, triptans, vestibular suppressants, and/or antiemetic agents may be considered. Pharmacologic migraine preventives (antiepileptics, beta-blockers, and antidepressants) are often useful. Conclusions: The keys to correctly diagnosing VM is identifying a relationship between vestibular symptoms and migrainous features and being aware of the heterogeneity of manifestations of this enigmatic, but treatable, condition. The principles of treatment of VM include rescue therapy, lifestyle modification, nonpharmacologic migraine preventives, pharmacologic migraine prophylaxis, and treatment of comorbidities.
Article
Background: Tinted lenses have been used to manage visual discomfort and photosensitivity in patients with migraines, benign essential blepharospasm (BEB) and epilepsy. Objectives: The purpose of this review is to examine the existing clinical research regarding the use of colored filters among patients recovering from traumatic brain injuries. Methods: A review of English articles from PubMed, Embase from embase.com, Web of Science, APA PsycINFO (OVID), Scopus, and Cochrane Central Register of Controlled Trials with publication years from date of inception to June 10, 2021 was performed. Articles were first screened by title and abstract, followed by full-text review. The search strategy resulted in 7819 results. The final analysis included seven articles which discussed the use of tinted lenses in patients post-traumatic brain injury. Results: While there is a paucity of information related to the therapeutic use of tinted lenses to mitigate post-traumatic light sensitivity and migraines, patients will subjectively report improved symptoms, specifically with precision tints or FL-41. Conclusion: Further studies are needed to understand the mechanism of action as well as objective and subjective benefits of tinted lenses in patient post-traumatic brain injury.
Article
Neurosensory deficits after traumatic brain injury can frequently lead to disability; therefore, diagnosis and treatment are important. Posttraumatic headaches typically resemble migraines and are managed similarly, but adjuvant physical therapy may be beneficial. Sleep-related issues are treated pharmacologically based on the specific sleep-related complaint. Fatigue is difficult to treat; cognitive behavioral therapy and aquatic therapy can be beneficial. Additionally, methylphenidate and modafinil have been used. Peripheral and central vestibular dysfunction causes dizziness and balance dysfunction, and the mainstay of treatment is vestibular physical therapy. Visual dysfunction incorporates numerous different diagnoses, which are frequently treated with specific rehabilitation programs.
Article
Background: Photophobia is a common sensory symptom after traumatic brain injury (TBI) that may have a grave impact on a patient's functional independence, neurorehabilitation, and activities of daily living. Post-TBI photophobia can be difficult to treat and the majority of patients can suffer chronically up to and beyond one year after their injury. Objectives: This review evaluates the current theories of the pathophysiology of photophobia and the most-common co-morbid etiologies of light sensitivity in TBI to help guide the differential diagnosis and individualized management of post-TBI photophobia. Methods: Primary articles were found via PubMed and Google Scholar search of key terms including "photophobia" "light sensitivity" "photosensitivity" "photo-oculodynia" "intrinsically photosensitive retinal ganglion cells" "ipRGC" and "concussion" "brain injury" "dry eye". Due to paucity of literature papers were reviewed from 1900 to present in English. Results: Recent advances in understanding the pathophysiology of photophobia in dry eye and migraine and their connection to intrinsically photosensitive retinal ganglion cells (ipRGC) have revealed complex and multifaceted trigeminovascular and trigeminoautonomic pathways underlying photophobia. Patients who suffer a TBI often have co-morbidities like dry eye and migraine that may influence the patient's photophobia. Conclusion: Post-traumatic photophobia is a complex multi-disciplinary complaint that can severely impact a patient's quality of life. Exploration of underlying etiology may allow for improved treatment and symptomatic relief for these patients beyond tinted lenses alone.
Article
Photophobia can affect a person’s quality of life. We present a case of idiopathic photophobia that was successfully managed with smart light bulbs that allowed the patient to participate in daily activities. Smart light can complement other treatment options including tinted lenses. In conclusion, smart light is a novel way of treating photophobia and should be considered by clinicians.
Article
Background: Primary headache disorders can cause many ophthalmic symptoms that lead many patients to present for neuro-ophthalmic evaluation. Neuro-ophthalmologists frequently encounter these patients in clinical practice. Evidence acquisition: A literature review was completed in PubMed using the following terms paired with "migraine" and "headache:" dry eye, eye pain, monocular diplopia, binocular diplopia, photophobia, visual field defect, tunnel vision, floaters, amaurosis fugax, transient visual obscuration, autonomic symptoms, anisocoria, visual snow, Alice in Wonderland syndrome, and palinopsia. Results: Patients with migraine experience a wide range of visual disturbances including aura and more complex perceptual abnormalities such as Alice in Wonderland syndrome and visual snow. Visual disturbances may consist of positive and/or negative phenomena and may be binocular or monocular. Migraine and other primary headache disorders can be associated with photophobia, eye pain, dry eye, autonomic features, and anisocoria. Conclusions: Patients with primary headache disorders may experience a wide range of visual and ophthalmic symptoms. An understanding of the typical features of these disorders allows providers to help patients find appropriate treatment without unnecessary testing and to recognize when atypical presentations require additional evaluation.
Article
Background Many individuals with migraine report symptoms of dry eye (DE). However, it is not known whether DE profiles are similar between individuals with and without migraine. To bridge this gap, we evaluated symptoms and signs of DE, including symptoms suggestive of nerve dysfunction, in a large group of individuals with DE symptoms, and compared profiles between individuals with migraine and those without migraine or headache. Methods Prospective cross-sectional study of individuals with DE symptoms seen at the Miami VA. Results Of 250 individuals, 31 met International Classification of Headache Disorders criteria for migraine based on a validated screen. Individuals with migraine were significantly younger (57 vs 62 years) and more likely to be female (26% vs 6%) than controls. Individuals with migraine had more severe DE symptoms and ocular pain compared with controls (mean Ocular Surface Disease Index 53.93 ± 21.76 vs 36.30 ± 22.90, p=0.0001; mean Neuropathic Pain Symptom Inventory modified for the Eye 39.39 ± 23.33 vs 21.86 ± 20.17, p=0.0001). The difference in symptom profile occurred despite similar ocular surface parameters between the groups. Conclusions Individuals with migraine had a different DE symptom yet a similar DE sign profile when compared with controls without migraine. This suggests that DE symptoms in individuals with migraine may be driven by nerve dysfunction as opposed to ocular surface abnormalities.
Article
Résumé Objectif Analyse des larmes de patients atteints de blépharospasme essentiel (BSE) afin d’explorer des mécanismes cornéo-conjonctivaux pouvant expliquer la photophobie, l’insuffisance lacrymale et les douleurs oculaires. Méthodes Sur une cohorte observationnelle de 42 patients atteints de blépharospasme essentiel, nous avons réalisé un test de Schirmer, une mesure du pH lacrymal, une électrophorèse des protéines lacrymales et une empreinte conjonctivale. Résultats Le test de Schirmer des patients objective une sécheresse lacrymale (8,4 ± 9,7 mm) avec 71,3 % des yeux ayant un Schirmer < 10 mm. Le pH lacrymal moyen de la cohorte est basique (8,4 ± 0,4) et est amélioré par le traitement de référence consistant en des injections trimestrielles de toxine botulique dans les paupières (8,32 ± 0,36 pour les patients traités vs 8,74 ± 0,53 pour les patients non traités ; p = 0,045). Ensemble, les électrophorèses des protéines lacrymales et les empreintes conjonctivales révèlent une inflammation conjonctivale associée au BSE. Conclusion Pour la première fois, cette étude apporte des arguments conjonctivaux objectifs pouvant en partie expliquer la photophobie, la sécheresse et les douleurs oculaires des patients atteints de BSE. Bien que ces résultats soient nouveaux et intéressants, des études complémentaires restent nécessaires pour évaluer l’efficacité de mesures correctives du pH et de l’inflammation lacrymale sur les symptômes oculaires et la qualité de vie des patients atteints de blépharospasme.
Article
Dry eye disease (DED) is a diagnosis given to individuals with a heterogeneous combination of symptoms and/or signs, including spontaneous and evoked ocular pain. Our current study evaluated whether and which ocular pain assessments could serve as screening tools for central sensitization in individuals with DED. A cohort of individuals with DED symptoms (n = 235) were evaluated for ocular pain, DED signs (tear production, evaporation), evoked sensitivity to mechanical stimulation at the cornea, and evidence of central sensitization. Central sensitization was defined for this study as the presence of pain 30 seconds after termination of a thermal noxious temporal summation protocol (ie, aftersensations) presented at a site remote from the eye (ventral forearm). We found that combining ratings of average intensity of ocular pain, ratings of average intensity of pain due to light, response to topical anesthetic eye drops, and corneal mechanical pain thresholds produced the best predictive model for central sensitization (area under the curve of .73). When examining ratings of intensity of ocular pain due to light alone (0–10 numerical rating), a cutoff score of 2 maximized sensitivity (85%) and specificity (48%) for the presence of painful aftersensations at the forearm. Self-reported rating of pain sensitivity to light may serve as a quick screening tool indicating the involvement of central nociceptive system dysfunction in individuals with DED. Perspective This study reveals that clinically-relevant variables, including a simple 0 to 10 rating of ocular pain due to light, can be used to predict the contribution of central sensitization mechanisms in a subgroup of individuals with DED symptoms. These findings can potentially improve patient stratification and management for this complex and painful disease.
Thesis
Ziel dieser Arbeit ist es, das menschliche Sehen unter Blendung zu erfassen. Zusätzlich soll ein Untersuchungsablauf erarbeitet werden, um Ursachen von Blendempfindlichkeit besser darstellen zu können.
Article
Purpose To evaluate the visual photosensitivity threshold and objective photosensitivity luminance in healthy eyes, thereby providing a normative dataset that will lead to a better understanding of diseases causing photophobia. Methods This was a prospective cross-sectional study. Emmetropes whose visual acuity was better than 0.18 logMAR (6/9) with no other ocular abnormality were included. Headache Impact Test-6 and visual light sensitivity questionnaires were administered. Visual photosensitivity threshold was measured subjectively using the ocular photosensitivity analyser. Objective photosensitivity luminance was assessed manually by evaluating videos recorded using an infrared camera and noting the intensity of light at the first squeezing reflex. Results Seventy five normal subjects (age range, 7–71 years) were included. Median age was 32.7 years (inter-quartile range, 20.3–47.9 years). Forty (53.3%) were males. Median Headache Impact Test score was 38 (inter-quartile range, 36–42) and visual light sensitivity questionnaire score was 11 (inter-quartile range, 8–15). Mean (standard deviation) right eye, left eye and binocular visual photosensitivity threshold was 3.34 (0.78), 3.33 (0.81) and 3.37 (0.78) loglux, respectively. There was a significant negative correlation of visual light sensitivity questionnaire scores with right eye, left eye and binocular visual photosensitivity thresholds, and positive correlation of age with binocular visual photosensitivity thresholds. Mean (standard deviation) right eye, left eye and binocular objective photosensitivity luminance was 3.25 (0.55), 3.35 (0.47) and 3.15 (0.52) loglux, respectively. Age was only positively correlated with binocular objective photosensitivity luminance, and there was no correlation between age and right eye or left eye objective photosensitivity luminance. Conclusions The study characterised, for the first time, objective photosensitivity luminance and established normative data for both visual photosensitivity threshold and objective photosensitivity luminance. The data will help in understanding the pathophysiology of diseases causing photophobia, monitoring the disease progression and evaluating treatment modalities.
Preprint
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Background: To present a simple method to evaluate transient eye closure (TEC) under bright light using binocular pupillometry in children with intermittent exotropia (IXT). Methods: Sixty-one children with IXT were studied using binocular pupillometry. Each patient was exposed to each phase as follows: scotopic phase (darkness) for 3,300 ms, mesopic phase for 200 ms, scotopic phase for 3,300 ms, low-intensity white light phase (10 cd/m²) for 200 ms, scotopic phase for 3,300 ms, and high-intensity white light phase (100 cd/m²) for 200 ms. TEC was present if the subject closed eyes immediately more than half in response to light, compared with the one in the scotopic phase. We assessed the agreement between TEC and self-reporting photosensitivity, and also evaluated the associated factors for the presence of TEC in IXT patients. Results: With the new method to evaluate TEC under different light intensities, 27 (44.3%) of the 61 IXT patients showed TEC, and 34 (55.7%) did not demonstrate TEC. TEC under high-intensity white light had a strong correlation with photosensitivity (r = 0.77). The smaller angle of deviation at near was associated with the presence of TEC, with statistical significance (p = 0.04). Normal sensory status at distance was significantly associated with TEC (p < 0.01). Multivariate analysis using multiple logistic regression analysis showed that normal sensory status was significantly associated with TEC (p = 0.02). Conclusions: The test using binocular pupillometry is useful in identifying TEC related to bright light, and the presence of TEC was strongly correlated with photosensitivity in patients with IXT.
Article
Full-text available
Purpose: Optical filters and tints manipulating short-wavelength light (sometimes called 'blue-blocking' or 'blue-attenuating' filters) are used in the management of a range of ocular, retinal, neurological and psychiatric disorders. In many cases, the only available quantification of the optical effects of a given optical filter is the spectral transmittance, which specifies the amount of light transmitted as a function of wavelength. Methods: We propose a novel physiologically relevant and retinally referenced framework for quantifying the visual and non-visual effects of these filters, incorporating the attenuation of luminance (luminous transmittance), the attenuation of melanopsin activation (melanopsin transmittance), the colour shift, and the reduction of the colour gamut (gamut reduction). Using these criteria, we examined a novel database of spectral transmittance functions of optical filters (n = 121) which were digitally extracted from a variety of sources. Results: We find a large diversity in the alteration of visual and non-visual properties. The spectral transmittance properties of the examined filters vary widely, in terms of shapes and cut-off wavelengths. All filters show relatively more melanopsin attenuation than luminance attenuation (lower melanopsin transmittance than luminous transmittance). Across the data set, we find that melanopsin transmittance and luminous transmittance are correlated. Conclusions: We suggest that future studies and examinations of the physiological effects of optical filters quantify the visual and non-visual effects of the filters beyond the spectral transmittance, which will eventually aid in developing a mechanistic understanding of how different filters affect physiology. We strongly discourage comparing the downstream effects of different filters on, e.g. sleep or circadian responses, without considering their effects on the retinal stimulus.
Article
Resumen Paciente mujer, de 54 años, con antecedente de fibromialgia y estudio preoperatorio ocular y sistémico normal, que presenta fotofobia invalidante de larga duración, tras cirugía bilateral secuencial de cataratas sin complicaciones. La fotofobia se acompañaba de buena AV no corregida, sin dolor ni molestias subjetivas oculares y sin migraña ni indicadores de conflictos psíquicos. Fue refractaria a cualquier tratamiento de la superficie ocular pautado, respondiendo finalmente a anticonvulsivantes orales (carbamazepina) frecuentemente utilizados en dolor de tipo neuropático. Según nuestro conocimiento es el único caso descrito de fotofobia invalidante de larga duración sin dolor y buena AV tras cirugía de cataratas.
Thesis
In our modern highly-illuminated world, symptoms of greater sensitivity to blue light increasingly appear. The impact of blue illumination on the ocular surface, the first barrier between the visual system and the external environment, is of particular interest. Since the crucial involvement of neurologic processes in ocular surface diseases such as dry eye is now widely recognized, the role of phototoxicity in neuro-ocular disorders is of great significance. The aim of this work was to investigate the potential harmful role of blue light in the context of dry eye and in relation to ocular nociception and light aversion. We demonstrated in vitro the phototoxic impact of blue light in human epithelial cells of the cornea and conjunctiva, and in neural and neuroglial cells from mouse trigeminal ganglia. In vivo, we reported that the significant aversion to blue light in mouse was accompanied by inflammation in the ocular surface and trigeminal pathways. We gave some insights into the ocular nociceptive pathways involved in photophobic mechanisms, together with the role of specific non-visual photoreceptors, melanopsin and neuropsin. This work sought to explain and corroborate frequent complaints about daily living increased photosensitivity in front of displays or under lightings rich in blue spectrum. Obtained results may therefore open new avenues for prevention and treatment of light-related ocular disorders and light aversion.
Chapter
Eyelid movement is neuroanatomically linked to eye movement, and thus eyelid abnormalities frequently accompany and sometimes precede or overshadow eye movement abnormalities in neurodegenerative disease. In this chapter, we summarize the various eyelid abnormalities that can occur in inherited and acquired neurodegenerative disorders in the context of the neuroanatomic pathways that are affected. The epidemiology and clinical approach to diagnosis and treatment of ptosis, eyelid retraction, abnormal spontaneous and reflexive blinking, blepharospasm, and eyelid apraxia will also be reviewed.
Article
Purpose: Pain is a frequently reported symptom in dry eye disease (DED). We examine the factors associated with ocular pain severity and patient-reported improvement in ocular pain to commonly used dry eye and pain treatments. Methods: Cross-sectional study of patients presenting for dry eye management. Demographics, ocular and medical history, OSDI, numeric pain scale, pain descriptors, and subjective response to tried eye drop, systemic, and non-pharmacologic treatments were collected. Statistical analysis was performed to identify differential treatment response in patients with various pain levels using the non-parametric test for trend. Results: 144 patients were categorized into 4 groups according to reported pain severity. Increasing pain was significantly associated with younger age, history of refractive surgery, higher OSDI score, and less likelihood of corneal staining. Patients with higher pain intensity were more likely to report a history of fibromyalgia, depression, anxiety, and migraine. Patients with greater pain severity were less responsive to treatment with artificial tears (p<0.001), lubricating ointment (p=0.002), steroid eye drops (p=0.03), cyclosporine 0.05% (p=0.03), 20% autologous serum tears (p=0.01), hot compresses (p=0.04), lid hygiene (p=0.002) and punctal occlusion (p=0.03). Conclusions: Dry eye patients with severe ocular pain often have associated psychological and systemic pain conditions. Treating the underlying DED is beneficial in reducing ocular pain, however the low rate of a satisfactory response highlights the need for further investigation of effective therapies. Cross-sectional studies can provide guidance in the treatment of patients with dry eye-related ocular pain and guide future prospective studies on potentially effective therapies.
Article
The case concerns a 54-year-old woman, with a history of fibromyalgia and normal preoperative ocular and systemic study, who presented with a long-lasting disabling photophobia, after sequential bilateral cataract surgery without complications. Photophobia was accompanied by good uncorrected VA, with no pain or subjective eye discomfort, without migraine or indicators of psychic conflict. It was refractory to any prescribed treatment of the ocular surface, finally responding to oral anticonvulsants (carbamazepine) that are frequently used in neuropathic pain. To the best of our knowledge this is the first reported case of a long-lasting disabling photophobia without pain and good VA after cataract surgery.
Article
Full-text available
Purpose Individuals receiving botulinum toxin A (BoNT-A) injections in the head and heck for migraine treatment have reported decreases in photophobia and sensations of dryness, independent of ocular surface parameters. We hypothesized that patients without migraine but with similar ocular neuropathic-like symptoms would also experience symptomatic improvement with periocular BoNT-A injections, independent of ocular surface changes. Observations We identified four individuals without a history of migraine but with neuropathic ocular pain (symptoms of dryness, burning, and photophobia that were out of proportion to ocular surface findings and unresponsive to ongoing dry eye (DE) therapies). Individuals underwent 1 session of periocular BoNT-A injections. Validated questionnaires (Visual Light Sensitivity Questionnaire-8, Dry Eye Questionnaire-5) assessed photophobia and DE symptoms pre- and 1-month post-injections. All four reported improvements in frequency and severity of photophobia and eye discomfort following BoNT-A injections. Tear film parameters (phenol red thread test, tear break-up time, corneal staining, and Schirmer test) and eyelid (palpebral fissure height and levator palpebrae superioris function) and eyebrow (position) anatomy were also evaluated before and after injections. Despite a unanimous improvement in symptoms, there were no consistent changes in ocular surface parameters with BoNT-A injections across individuals. Conclusions and Importance: Periocular BoNT-A shows promise in reducing photophobia and sensations of dryness in individuals with neuropathic-like DE symptoms without a history of migraine, independent of tear film, eyelid, or eyebrow parameters.
Chapter
Photophobia is one of the most common visual complaints stemming from mild traumatic brain injury (mTBI) and causes significant distress. Despite extensive research, the etiology of photophobia is poorly understood, and symptoms are difficult to treat. No randomized controlled trials of treatment of photophobia in patients with mTBI exist; however, tinted glasses have been tried with some success. Targeted therapies involving infusion of calcium gene-related peptide antibody may hold promise.
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As the biological alarm of impending or actual tissue damage, pain is essential for our survival. However, when it is initiated and/or sustained by dysfunctional elements in the nociceptive system, it is itself a disease known as neuropathic pain. While the critical nociceptive system provides a number of protective functions, it is unique in its central role of monitoring, preserving and restoring the optical tear film in the face of evaporative attrition without which our vision would be non-functional. Meeting this existential need resulted in the evolution of the highly complex, powerful and sensitive dry eye alarm system integrated in the peripheral and central trigeminal sensory network. The clinical consequences of corneal damage to these nociceptive pathways are determined by the type and location of its pathological elements and can range from the spectrum known as dry eye disease to the centalised oculofacial neuropathic pain syndrome characterised by a striking disparity between the high intensity of symptoms and paucity of external signs. These changes parallel those observed in somatic neuropathic pain. When seen through the neuroscience lens, diseases responsible for inadequately explained chronic eye pain (including those described as dry eye) can take on new meanings that may clarify long-standing enigmas and point to new approaches for developing preventive, symptomatic and disease-modifying interventions for these currently refractory disorders. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.
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To analyze the density and morphology of corneal epithelial cells and keratocytes by in vivo confocal microscopy (IVCM) in patients with herpes zoster ophthalmicus (HZO) as associated with corneal innervation. Prospective, controlled and masked cross-sectional study. Setting: Single center study. Patients: Thirty eyes with the diagnosis HZO and their contralateral clinically unaffected eyes, fifteen eyes of 15 normal controls. Intervention procedures: In vivo confocal microscopy and corneal esthesiometry of the central cornea. Main Outcome Measures: Changes in morphology and density of the superficial and basal epithelial cells, stromal keratocytes and correlation with corneal sensation, number of nerves, and total length of nerves. The density of superficial epithelial cells in HZO eyes with severe sensation loss (766.5±25.2 cells/mm(2)) was significantly lower than both healthy control eyes (1450.23±150.83 cells/mm(2)) and contralateral unaffected eyes (1974±298.24 cells/mm(2)). (p=0.003). Superficial epithelial cell size (1162.5 μm(2)) was significantly larger in HZO eyes with severe loss of sensation, as compared to contralateral (441.46 ± 298.14) or healthy eyes (407.4 μm(2); all p<0.05). The density of basal epithelial cells, anterior keratocytes, and posterior keratocytes did not show statistical significance between patients, controls and contralateral unaffected eyes. Changes in superficial epithelial cell density and morphology correlated strongly with corneal sensation. In vivo confocal microscopy reveals profound HZO-induced changes in the superficial epithelium, as demonstrated by increase in cell size, decrease in cell density, and squamous metaplasia. We demonstrate that these changes strongly correlate with changes in corneal innervation in eyes affected by HZO. Copyright © 2015 Elsevier Inc. All rights reserved.
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Many adult outpatients with attention-deficit/hyperactivity disorder (ADHD) report an oversensitivity to light. We explored the link between ADHD and photophobia in an online survey (N = 494). Self-reported photophobia was prevalent in 69% of respondents with, and in 28% of respondents without, ADHD (symptoms). The ADHD (symptoms) group wore sunglasses longer during daytime in all seasons. Photophobia may be related to the functioning of the eyes, which mediate dopamine and melatonin production systems in the eye. In the brain, dopamine and melatonin are involved in both ADHD and circadian rhythm disturbances. Possibly, the regulation of the dopamine and melatonin systems in the eyes and in the brain are related. Despite the study’s limitations, the results are encouraging for further study on the pathophysiology of ADHD, eye functioning, and circadian rhythm disturbances.
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Neurons in the mammalian retina expressing the photopigment melanopsin have been identified as a class of intrinsically photosensitive retinal ganglion cells (ipRGCs). This discovery more than a decade ago has opened up an exciting new field of retinal research, and following the initial identification of photosensitive ganglion cells, several subtypes have been described. A number of studies have shown that ipRGCs subserve photoentrainment of circadian rhythms. They also influence other non-image forming functions of the visual system, such as the pupillary light reflex, sleep, cognition, mood, light aversion and development of the retina. These novel photosensitive neurons also influence form vision by contributing to contrast detection. Furthermore, studies have shown that ipRGCs are more injury-resistant following optic nerve injury, in animal models of glaucoma, and in patients with mitochondrial optic neuropathies, i.e., Leber's hereditary optic neuropathy and dominant optic atrophy. There is also an indication that these cells may be resistant to glutamate-induced excitotoxicity. Herein we provide an overview of ipRGCs and discuss the injury-resistant character of these neurons under certain pathological and experimental conditions. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.
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This is to our knowledge the first systematic review regarding the efficacy of manual therapy randomized clinical trials (RCT) for primary chronic headaches. A comprehensive English literature search on CINHAL, Cochrane, Medline, Ovid and PubMed identified 6 RCTs all investigating chronic tension-type headache (CTTH). One study applied massage therapy and five studies applied physiotherapy. Four studies were considered to be of good methodological quality by the PEDro scale. All studies were pragmatic or used no treatment as a control group, and only two studies avoided co-intervention, which may lead to possible bias and makes interpretation of the results more difficult. The RCTs suggest that massage and physiotherapy are effective treatment options in the management of CTTH. One of the RCTs showed that physiotherapy reduced headache frequency and intensity statistical significant better than usual care by the general practitioner. The efficacy of physiotherapy at post-treatment and at 6 months follow-up equals the efficacy of tricyclic antidepressants. Effect size of physiotherapy was up to 0.62. Future manual therapy RCTs are requested addressing the efficacy in chronic migraine with and without medication overuse. Future RCTs on headache should adhere to the International Headache Society's guidelines for clinical trials, i.e. frequency as primary end-point, while duration and intensity should be secondary end-point, avoid co-intervention, includes sufficient sample size and follow-up period for at least 6 months.
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Light is a powerful stimulant for human alertness and cognition, presumably acting through a photoreception system that heavily relies on the photopigment melanopsin. In humans, evidence for melanopsin involvement in light-driven cognitive stimulation remains indirect, due to the difficulty to selectively isolate its contribution. Therefore, a role for melanopsin in human cognitive regulation remains to be established. Here, sixteen participants underwent consecutive and identical functional MRI recordings, during which they performed a simple auditory detection task and a more difficult auditory working memory task, while continuously exposed to the same test light (515 nm). We show that the impact of test light on executive brain responses depends on the wavelength of the light to which individuals were exposed prior to each recording. Test-light impact on executive responses in widespread prefrontal areas and in the pulvinar increased when the participants had been exposed to longer (589 nm), but not shorter (461 nm), wavelength light, more than 1 h before. This wavelength-dependent impact of prior light exposure is consistent with recent theories of the light-driven melanopsin dual states. Our results emphasize the critical role of light for cognitive brain responses and are, to date, the strongest evidence in favor of a cognitive role for melanopsin, which may confer a form of "photic memory" to human cognitive brain function.
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The weekly incidence of headaches among office workers was compared when the offices were lit by fluorescent lighting where the fluorescent tubes were operated by (a) a conventional switch-start circuit with choke ballast providing illumination that pulsated with a modulation depth of 43-49% and a principal frequency component at 100 Hz; (b) an electronic start circuit with choke ballast giving illumination with similar characteristics; (c) an electronic ballast driving the lamps at about 32 kHz and reducing the 100 Hz modulation to less than 7%. In a double-blind cross-over design, the average incidence of headaches and eyestrain was more than halved under high-frequency lighting. The incidence was unaffected by the speed with which the tubes ignited. Headaches tended to decrease with the height of the office above the ground and thus with increasing natural light. Office occupants chose to switch on the high-frequency lighting for 30% longer on average.
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Melanopsin-expressing intrinsically photosensitive retinal ganglion cells (ipRGCs) are the only functional photoreceptive cells in the eye of newborn mice. Through postnatal day 9, in the absence of functional rods and cones, these ipRGCs mediate a robust avoidance behavior to a light source, termed negative phototaxis. To determine whether this behavior is associated with an aversive experience in neonatal mice, we characterized light-induced vocalizations and patterns of neuronal activation in regions of the brain involved in the processing of aversive and painful stimuli. Light evoked distinct melanopsin-dependent ultrasonic vocalizations identical to those emitted under stressful conditions, such as isolation from the litter. In contrast, light did not evoke the broad-spectrum calls elicited by acute mechanical pain. Using markers of neuronal activation, we found that light induced the immediate-early gene product Fos in the posterior thalamus, a brain region associated with the enhancement of responses to mechanical stimulation of the dura by light, and thought to be the basis for migrainous photophobia. Additionally, light induced the phosphorylation of extracellular-related kinase (pERK) in neurons of the central amygdala, an intracellular signal associated with the processing of the aversive aspects of pain. However, light did not activate Fos expression in the spinal trigeminal nucleus caudalis, the primary receptive field for painful stimulation to the head. We conclude that these light-evoked vocalizations and the distinct pattern of brain activation in neonatal mice are consistent with a melanopsin-dependent neural pathway involved in processing light as an aversive but not acutely painful stimulus.
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SYNOPSIS In a questionnaire survey we determined the prevalence of visual symptoms and eye strain factors in a group of chronic headache sufferers as compared with age- and sex-matched controls. The visual symptoms studied were those not pecific for headache, i.e., sensitivity to light and blurred vision. Sensitivity to light in the absence of headache was reported by 27.8% of controls and 44.7% of headache sufferers (p<0.05). The latter figure increased to 71.3% when headache was actually present (p<0.001). Blurred vision occurred in 13.5% of controls and 7.4% of headache sufferers (not significant). In the presence of headache, the latter figure increased to 44.7% (p< 0.01). Of the eye strain factors studied, bright light was reported to precipitate headache in 29.3% and to aggravate it in 73.4%. For reading, these figures were 16.0% and 55.3%, respectively; for working at the computer screen, 14.5% and 31.3%; and for watching television, 6.4% and 27.7%. We conclude that visual symptoms are more common in chronic headache and eye strain factors more important than is generally recognized.
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Certain patterns can induce perceptual illusions/distortions and visual discomfort in most people, headaches in patients with migraine, and seizures in patients with photosensitive epilepsy. Visual stimuli are common triggers for migraine attacks, possibly because of a hyperexcitability of the visual cortex shown in patients with migraine. Precision ophthalmic tints (POTs) are claimed to reduce perceptual distortions and visual discomfort and to prevent migraine headaches in some patients. We report an fMRI visual cortical activation study designed to investigate neurological mechanisms for the beneficial effects of POTs in migraine. Eleven migraineurs and 11 age- and sex-matched non-headache controls participated in the study using non-stressful and stressful striped patterns viewed through gray, POT, and control coloured lenses. For all lenses, controls and migraineurs did not differ in their response to the non-stressful patterns. When the migraineurs wore gray lenses or control coloured lenses, the stressful pattern resulted in activation that was greater than in the controls. There was also an absence of the characteristic low-pass spatial frequency (SF) tuning in extrastriate visual areas. When POTs were worn, however, both cortical activation and SF tuning were normalized. Both when observing the stressful pattern and under more typical viewing conditions, the POTs reduced visual discomfort more than either of the other two lenses. The normalization of cortical activation and SF tuning in the migraineurs by POTs suggests a neurological basis for the therapeutic effect of these lenses in reducing visual cortical hyperactivation in migraine.
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Corneal confocal microscopy is a growing technique for the study of the cornea at the cellular level, providing images comparable to ex vivo histochemical methods. In vivo confocal microscopy (IVCM) has an enormous potential, being a noninvasive procedure that images the living cornea, to study both its physiological and pathological states. Corneal nerves are of great interest to clinicians and scientists due to their important roles in regulating corneal sensation, epithelial integrity, proliferation, wound healing, and for their protective functions. IVCM enables the noninvasive examination of corneal nerves, allowing the study of nerve alterations in different ocular diseases, after corneal surgery, and in systemic diseases. To date, the correlation of sub-basal corneal nerves and their function has been studied in normal eyes, keratoconus, dry eye, contact lens wearers, and in neurotrophic keratopathy, among others. Further, the effect of corneal surgery on nerves has been studied, demonstrating the regenerative capacity of corneal nerves and the recovery of sensation. Moreover, IVCM has been applied in the diagnosis of peripheral diabetic neuropathy and the assessment of progression in this systemic disease. The purpose of this review is to describe the principles, applications, and clinical correlation of IVCM in the study of corneal nerves in different ocular and systemic diseases.
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Alterations in cortical excitability are implicated in the pathophysiology of migraine. However, the relationship between cortical spreading depression (CSD) and headache has not been fully elucidated. We aimed to identify the corticofugal networks that directly influence meningeal nociception in the brainstem trigeminocervical complex (Sp5C) of the rat. Cortical areas projecting to the brainstem were first identified by retrograde tracing from Sp5C areas that receive direct meningeal inputs. Anterograde tracers were then injected into these cortical areas to determine the precise pattern of descending axonal terminal fields in the Sp5C. Descending cortical projections to brainstem areas innervated by the ophthalmic branch of the trigeminal nerve originate contralaterally from insular (Ins) and primary somatosensory (S1) cortices and terminate in laminae I-II and III-V of the Sp5C, respectively. In another set of experiments, electrophysiological recordings were simultaneously performed in Ins, S1 or primary visual cortex (V1), and Sp5C neurons. KCl was microinjected into such cortical areas to test the effects of CSD on meningeal nociception. CSD initiated in Ins and S1 induced facilitation and inhibition of meningeal-evoked responses, respectively. CSD triggered in V1 affects differently Ins and S1 cortices, enhancing or inhibiting meningeal-evoked responses of Sp5C, without affecting cutaneous-evoked nociceptive responses. Our data suggest that "top-down" influences from lateralized areas within Ins and S1 selectively affect interoceptive (meningeal) over exteroceptive (cutaneous) nociceptive inputs onto Sp5C. Such corticofugal influences could contribute to the development of migraine pain in terms of both topographic localization and pain tuning during an attack.
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Photophobia is an abnormal sensitivity to light experienced by migraineurs and is perhaps caused by cortical hyperexcitability. In clinical studies, an inter-relation between light perception and trigeminal nociception has been demonstrated in migraineurs but not in controls. The purpose of the study was to verify this interaction by functional imaging. The authors used H(2)O(15) positron emitting tomography (PET) to study the cortical responses of seven migraineurs between attacks and the responses of seven matched control subjects to luminous stimulations at three luminance intensities: 0, 600 and 1800 Cd/m(2). All three intensities were both with and without concomitant trigeminal pain stimulation. In order to facilitate habituation, the stimulations were started 30 s before PET acquisitions. When no concomitant pain stimulation was applied, luminous stimulations activated the visual cortex bilaterally in migraineurs (specifically in the cuneus, lingual gyrus and posterior cingulate cortex) but not in controls. Concomitant pain stimulation allowed visual cortex activation in control subjects and potentiated its activation in migraineurs. These activations by luminous stimulations were luminance-intensity-dependent in both groups. Concomitant stimulation by pain was associated with activation of the posterior parietal cortex (BA7) in migraineurs and controls. The study shows the lack of habituation and/or cortical hyperexcitability to light in migraineurs. Moreover, the activation by light of several visual cortex areas (including the primary visual cortex) was potentiated by trigeminal pain, demonstrating multisensory integration in these areas.
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The perception of migraine headache, which is mediated by nociceptive signals transmitted from the cranial dura mater to the brain, is uniquely exacerbated by exposure to light. We found that exacerbation of migraine headache by light is prevalent among blind individuals who maintain non-image-forming photoregulation in the face of massive rod/cone degeneration. Using single-unit recording and neural tract tracing in the rat, we identified dura-sensitive neurons in the posterior thalamus whose activity was distinctly modulated by light and whose axons projected extensively across layers I-V of somatosensory, visual and associative cortices. The cell bodies and dendrites of such dura/light-sensitive neurons were apposed by axons originating from retinal ganglion cells (RGCs), predominantly from intrinsically photosensitive RGCs, the principle conduit of non-image-forming photoregulation. We propose that photoregulation of migraine headache is exerted by a non-image-forming retinal pathway that modulates the activity of dura-sensitive thalamocortical neurons.
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Light therapy is increasingly applied in a variety of sleep medicine and psychiatric conditions including circadian rhythm sleep disorders, seasonal affective disorder, and dementia. This article reviews the neural underpinnings of circadian neurobiology crucial for understanding the influence of light therapy on brain function, common mood and sleep disorders in which light therapy may be effectively used, and applications of light therapy in clinical practice.
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In addition to rods and cones, the human retina contains light-sensitive ganglion cells that express melanopsin, a photopigment with signal transduction mechanisms similar to that of invertebrate rhabdomeric photopigments (IRP). Like fly rhodopsins, melanopsin acts as a dual-state photosensitive flip-flop in which light drives both phototransduction responses and chromophore photoregeneration that bestows independence from the retinoid cycle required by rods and cones to regenerate photoresponsiveness following bleaching by light. To explore the hypothesis that melanopsin in humans expresses the properties of a bistable photopigment in vivo we used the pupillary light reflex (PLR) as a tool but with methods designed to study invertebrate photoreceptors. We show that the pupil only attains a fully stabilized state of constriction after several minutes of light exposure, a feature that is consistent with typical IRP photoequilibrium spectra. We further demonstrate that previous exposure to long wavelength light increases, while short wavelength light decreases the amplitude of pupil constriction, a fundamental property of IRP difference spectra. Modelling these responses to invertebrate photopigment templates yields two putative spectra for the underlying R and M photopigment states with peaks at 481 nm and 587 nm respectively. Furthermore, this bistable mechanism may confer a novel form of "photic memory" since information of prior light conditions is retained and shapes subsequent responses to light. These results suggest that the human retina exploits fly-like photoreceptive mechanisms that are potentially important for the modulation of non-visual responses to light and highlights the ubiquitous nature of photoswitchable photosensors across living organisms.
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To describe the magnitude and distribution of the public health problem posed by migraine in the United States by examining migraine prevalence, attack frequency, and attack-related disability by gender, age, race, household income, geographic region, and urban vs rural residence. In 1989, a self-administered questionnaire was sent to a sample of 15,000 households. A designated member of each household initially responded to the questionnaire. Each household member with severe headache was asked to respond to detailed questions about symptoms, frequency, and severity of headaches. A sample of households selected from a panel to be representative of the US population in terms of age, gender, household size, and geographic area. After a single mailing, 20,468 subjects (63.4% response rate) between 12 and 80 years of age responded to the survey. Respondents and non-respondents did not differ by gender, household income, region of the country, or urban vs rural status. Whites and the elderly were more likely to respond. Migraine headache cases were identified on the basis of reported symptoms using established diagnostic criteria. 17.6% of females and 5.7% of males were found to have one or more migraine headaches per year. The prevalence of migraine varied considerably by age and was highest in both men and women between the ages of 35 to 45 years. Migraine prevalence was strongly associated with household income; prevalence in the lowest income group (less than $10,000) was more than 60% higher than in the two highest income groups (greater than or equal to $30,000). The proportion of migraine sufferers who experienced moderate to severe disability was not related to gender, age, income, urban vs rural residence, or region of the country. In contrast, the frequency of headaches was lower in higher-income groups. Attack frequency was inversely related to disability. A projection to the US population suggests that 8.7 million females and 2.6 million males suffer from migraine headache with moderate to severe disability. Of these, 3.4 million females and 1.1 million males experience one or more attacks per month. Females between ages 30 to 49 years from lower-income households are at especially high risk of having migraines and are more likely than other groups to use emergency care services for their acute condition.
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Previous evidence suggests optical treatments hold promise for treating migraine and photophobia. We designed an optical notch filter, centered at 480nm to reduce direct stimulation of intrinsically photosensitive retinal ganglion cells. We used thin-film technology to integrate the filter into spectacle lenses. Our objective was to determine if an optical notch filter, designed to attenuate activity of intrinsically photosensitive retinal ganglion cells, could reduce headache impact in chronic migraine subjects. For this randomized, double-masked study, our primary endpoint was the Headache Impact Test (HIT-6; GlaxoSmithKline, Brentford, Middlesex, UK). We developed two filters: the therapeutic filter blocked visible light at 480nm; a 620nm filter was designed as a sham. Participants were asked to wear lenses with one of the filters for 2weeks; after 2weeks when no lenses were worn, they wore lenses with the other filter for 2weeks. Of 48 subjects, 37 completed the study. Wearing either the 480 or 620nm lenses resulted in clinically and statistically significant HIT-6 reductions. However, there was no significant difference when comparing overall effect of the 480 and 620nm lenses. Although the 620nm filter was designed as a sham intervention, research published following the trial indicated that melanopsin, the photopigment in intrinsically photosensitive retinal ganglion cells, is bi-stable. This molecular property may explain the unexpected efficacy of the 620nm filter. These preliminary findings indicate that lenses outfitted with a thin-film optical notch filter may be useful in treating chronic migraine.
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We used in vivo corneal confocal microscopy to investigate structural differences in the sub-basal corneal nerve plexus in chronic migraine patients and a normal population. We used a validated questionnaire and tests of lacrimal function to determine the prevalence of dry eye in the same group of chronic migraine patients. Activation of the trigeminal system is involved in migraine. Corneal nociceptive sensation is mediated by trigeminal axons that synapse in the gasserian ganglion and the brainstem, and serve nociceptive, protective, and trophic functions. Noninvasive imaging of the corneal sub-basal nerve plexus is possible with in vivo corneal confocal microscopy.
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Migraine is a complex and multifactorial brain disorder affecting approximately 18% of women and 5% of men in the United States, costing billions of dollars annually in direct and indirect healthcare costs and school and work absenteeism and presenteeism. Until this date, there have been no medications that were designed with the specific purpose to decrease the number of migraine attacks, which prompts a search for alternative interventions that could be valuable, such as acupuncture. Acupuncture origins from ancient China and encompasses procedures that basically involve stimulation of anatomical points of the body. This manuscript reviews large and well-designed trials of acupuncture for migraine prevention and also the effectiveness of acupuncture when tried against proven migraine preventative medications. Acupuncture seems to be at least as effective as conventional drug preventative therapy for migraine and is safe, long lasting, and cost-effective. It is a complex intervention that may prompt lifestyle changes that could be valuable in patients' recovery. © 2015 American Headache Society.
Article
Background Over the past 4000 years, acupuncture has survived the test of time. Recent scientific studies posit acupuncture is an effective intervention for back and joint pain and headache, including migraine.Methods The process of acupuncture is explained, including the role of Qi, the integration of Yang and Yin, the 5 elements, the 8 trigrams, and the metaphors that help the acupuncturist understand the patient, interpret symptoms, and determine acupuncture points in the meridians used to prevent or treat disease. A case study is presented from 3 perspectives: allopathic, traditional acupuncture, and Western acupuncture.ResultsSelected acupuncture studies in headache are reviewed. The safety of acupuncture is discussed as well as the challenges in conducting clinical studies of acupuncture.
Article
Objective. —To describe the magnitude and distribution of the public health problem posed by migraine in the United States by examining migraine prevalence, attack frequency, and attack-related disability by gender, age, race, household income, geographic region, and urban vs rural residence.Design. —In 1989, a self-administered questionnaire was sent to a sample of 15000 households. A designated member of each household initially responded to the questionnaire. Each household member with severe headache was asked to respond to detailed questions about symptoms, frequency, and severity of headaches.Setting. —A sample of households selected from a panel to be representative of the US population in terms of age, gender, household size, and geographic area.Participants. —After a single mailing, 20468 subjects (63.4% response rate) between 12 and 80 years of age responded to the survey. Respondents and non-respondents did not differ by gender, household income, region of the country, or urban vs rural status. Whites and the elderly were more likely to respond. Migraine headache cases were identified on the basis of reported symptoms using established diagnostic criteria.Results. —17.6% of females and 5.7% of males were found to have one or more migraine headaches per year. The prevalence of migraine varied considerably by age and was highest in both men and women between the ages of 35 to 45 years. Migraine prevalence was strongly associated with household income; prevalence in the lowest income group (<$10 000) was more than 60% higher than in the two highest income groups (≥$30 000). The proportion of migraine sufferers who experienced moderate to severe disability was not related to gender, age, income, urban vs rural residence, or region of the country. In contrast, the frequency of headaches was lower in higher-income groups. Attack frequency was inversely related to disability.Conclusions. —A projection to the US population suggests that 8.7 million females and 2.6 million males suffer from migraine headache with moderate to severe disability. Of these, 3.4 million females and 1.1 million males experience one or more attacks per month. Females between ages 30 to 49 years from lower-income households are at especially high risk of having migraines and are more likely than other groups to use emergency care services for their acute condition.(JAMA. 1992;267:64-69)
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Objective Post-traumatic headache (PTH) of the migraine type is a common complication of mild traumatic brain injury (including blast injuries) in active duty service members. Persistent and near-daily headache occur. Usual preventive medications may have unacceptable side effects. Anecdotal reports suggest that onabotulinum toxin A (OBA) might be an effective treatment in these patients.Methods This study is a real-time retrospective consecutive case series of all patients treated with OBA at the Concussion Care Clinic of Womack Army Medical Center, Ft. Bragg, NC, between August 2008 and August 2012. Clinical treatment and pharmacy records were corroborated with the electronic medical records in the Armed Forces Health Longitudinal Technology Application to determine demographics, current headache and treatment characteristics, and clinical and occupational outcomes.ResultsSixty-four subjects (63 male) with mean age of 31.3 + 7.5 (range 20-59) years were evaluated and treated. Blast injuries were most common (n = 36; 56.3%) and 7 patients (11%) reported a prior history of headache. Most patients (36; 56.3%) described more than 1 headache type and 48 (75%) patients had continuous pain. The most prevalent treating diagnosis was mixed continuous headache with migraine features on more than 15 days per month (n = 26; 40.6%). The mean time from injury to the first injections was 10.8 + 21.9 (1-96) months. Forty (62.5%) patients received the Food and Drug Administration-approved chronic migraine injection protocol. Forty-one (64%) patients reported being better. Two patients discontinued for side effects. Twenty-seven (41%) remained on active duty.Conclusions We demonstrate that active duty military patients with headaches related to concussions may benefit from treatment with OBA. Further studies are indicated.
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To investigate causes, associations, and results of treatment with blepharospasm, 1,653 patients were evaluated by extensive questionnaires to study blepharospasm and long-term results of treatment with the full myectomy operation, botulinum-A toxin, drug therapy, and help from the Benign Essential Blepharospasm Research Foundation (BEBRF). The percent of patients improved by the BEBRF was 90%, full myectomy 88%, botulinum-A toxin 86%, and drug therapy 43%. The patient acceptance rate for the BEBRF was 96%, full myectomy 82%, botulinum-A toxin 95%, and drug therapy 57%. Blepharospasm is multifactorial in origin and manifestation. A vicious cycle and defective circuit theory to explain origin and direct treatment rather than a defective specific locus is presented. All four forms of therapy evaluated are useful and must be tailored to the patient's needs. Mattie Lou Koster and the BEBRF have helped blepharospasm sufferers more than any other modality, and all patients should be informed of this support group. The full myectomy is reserved for botulinum-A toxin failures, and the limited myectomy is an excellent adjunct to botulinum-A toxin. (C)1998The American Society of Opthalmic Plastic and Reconstructive Surgery, Inc.
Article
Background Migraine equivalents are common clinical conditions without headache component, occurring as repeated attacks with complete remission between episodes. They include abdominal migraine, cyclical vomiting, benign paroxysmal vertigo, and benign paroxysmal torticollis. Other clinical entities, such as motion sickness and limb pain have been associated with migraine. We aimed to investigate the migraine equivalents prevalence in a large population of children referred to a pediatric headache centre and to reveal a possible relationship between migraine equivalents and headache features. Methods A total of 1.134 of children/adolescents (73.2% with migraine and 26.8% with tension-type headache) was included. Patients were divided into two groups according to the attack frequency (high and low). Pain intensity was rated on a 3-levels graduate scale (mild, moderate and severe pain). Results Migraine equivalents were reported in 70.3% of patients. Abdominal migraine (48.9%), limb pain (43.9%), and motion sickness (40.5%) were the most common migraine equivalents. While headache type (migraine or tension-type headache) did not correlate with migraine equivalents presence (χ2=33.2; P=0.27), high frequency of headache attacks correlated with migraine equivalents presence. Moreover, migraine equivalents showed a protective role for some accompanying symptom of the headache attack. Conclusions Our results suggest that migraine equivalents should not be considered merely as headache precursors, but they are part of the migrainous syndrome. Thus, their inclusion among the diagnostic criteria for pediatric migraine/tension-type headache is hopeful.
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