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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... 9 A recent study reported short TBUT and superficial punctate keratitis as risk factors for photophobia (OR 1.8). 4 Hence, the two principal components of photophobia in DED are ocular surface irregularity and central sensitization. [10][11][12] It is well established that there is discordance between symptoms and signs in DED patients. 1 It is unclear if photophobia is associated with the tear film changes. ...
... Photophobia can have ocular and non-ocular etiologies ranging from migraine to corneal scarring and retinal pathologies to traumatic brain injury. 11,12 Buchanan et al. reported migraine headache (53.7%) to be the most common cause of photophobia, followed by DED (36.1%), ocular trauma (8.2%), progressive supranuclear palsy (6.8%), and traumatic brain injury (4.1%). 12 Ocular surface conditions like DED and corneal neuropathy are seen post viral keratitis, and diabetic neuropathy is associated with photophobia. ...
... 10 Photosensitive retinal ganglion cells initiate the photophobia signaling to the brain. 11 Functional MRI study of photophobic patients with minimal to severe DED showed more robust activation of the occipital cortex compared to controls. 6 There is hyperactivity in the cortical visual system and abnormal interactions between visual areas and within the cortex of DED patients. ...
Article
Purpose: To assess the tear film parameters associated with photophobia in dry eye disease (DED). Methods: Three hundred seventy-four patients with DED (mean age, 42.2 ± 12.8 years) had their tear film and OSDI scores evaluated using Oculus keratograph 5 M (TMH, NIBUT, Meibography), Lipiview interferometer (LLT), and TearLab osmolarity system. Photophobia scoring from OSDI sheets was used to calculate the odds ratio via multivariate logistic regression analysis. Data from the eye with severely affected NIBUT was used. Results: Of 374, 127 had aqueous deficient dry eye disease (ADDE), and 247 had evaporative DED. The mean age, female sex, Schirmer I, TMH, NIBUT, LLT, and tear osmolarity values in patients with photophobia versus no or mild photophobia were 42.2. vs. 40.9 years, 42% vs. 40%, 11.6 vs. 10.5 mm, 0.27 vs. 0.29 mm, 4.6 vs. 4.7s, 60.3 vs. 60.9 nm and 305 vs. 307 mOsm/L, respectively. Multivariate analysis revealed no tear film parameters predictive of photophobia in evaporative DED, whereas tear osmolarity had a weak negative association with photophobia (odds ratio of 0.96, 95% C.I, 0.92-1, p = .04) in ADDE patients. Conclusion: Tear film parameters do not predict the presence or absence of photophobia in DED except for a weak inverse association with tear osmolarity in ADDE. This suggests the role of central sensitization in regulating photophobia in DED patients.
... Photophobia is defined as an abnormal intolerance to normal light levels. [16][17][18] Photophobia is probably a response to protect the retina from the light stimulus, as the threshold is lowered from baseline after concussion. [18,19] Photophobia is one the most common symptoms in both acute and chronic phases of concussion. ...
... [16][17][18] Photophobia is probably a response to protect the retina from the light stimulus, as the threshold is lowered from baseline after concussion. [18,19] Photophobia is one the most common symptoms in both acute and chronic phases of concussion. It has gained more attention in recent years, partly because of the number of veterans returning from Iraq and Afghanistan with TBI and the increased awareness of sports-related TBI. ...
... [23] A large contribution to prolonged post-traumatic photophobia may be related to the comorbidity of migraine-like headache after TBI. [18] Furthermore, patients tend to be particularly sensitive to artificial indoor light and all kinds of electronic screens. [18] Patients often need to dim the light intensity or modify the hue settings. ...
Article
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Purpose of Review Concussion frequently results in visual symptoms, necessitating careful neuro-ophthalmic examination. Both afferent and efferent visual systems are sensitive to brain injury. The present review focuses on the pathophysiology, clinical presentations, examinations, management, and future directions regarding visual disturbances after concussion. Recent Findings Photophobia is common in both acute and chronic concussion. Abnormalities of accommodation, convergence, saccades, and smooth pursuits can result in blurred vision, double vision, and difficulty with near work. Vision-based testing is crucial in the detection of concussion. Retinal nerve fiber layer thickness measurement may elucidate the risk of structural and functional sequelae. Patients presented with visual field loss or cranial neuropathies require evaluation for structural lesions. Summary Proper neuro-ophthalmic examination is instrumental in clinical decision-making for the diagnosis and management of concussion, as well as directing future investigations on preventing long-term complications.
... The rationale that Katz and Digre 23 give for the benefit from the modern FL-41 illustrated in the right panel of Figure 11.8 is that this reduces excitation of the intrinsically photosensitive retinal ganglion cells. These photoreceptors were linked to photophobia in 2010 by Noseda and colleagues. ...
... Transmission curves of original FL41 (left) and one of the modern FL-41 (right) tints. The left graph is reproduced under STM Permissions Guidelines from Wilkins and Wilkinson 19 and the right graph is reproduced under STM Permissions Guidelines from Katz and Digre.23 ...
Chapter
In this chapter we review studies in which precision tints have been used in a variety of neurological disorders, including photosensitive epilepsy, autism, migraine, cluster headache, visual snow, stroke, multiple sclerosis and concussion (mild brain trauma). Whilst the evidence regarding these topics is preliminary and indicative, the effects of coloured filters in these conditions may help to further elucidate the mechanisms underlying the benefit from colour. In particular, the extent to which these findings provide convergent support for the cortical hyperexcitability hypothesis is discussed.
... Photophobia is defined broadly as a sensory state in which light causes discomfort or pain in the eye or head, or that light causes an avoidance reaction (e.g., seeking to be or remain in darkness), even without the presence of overt pain (Digre & Brennan, 2012;Katz & Digre, 2016). If protective blinking evolved with the first terrestrial vertebrates 375 M years ago (Aiello et al., 2023), if ipRGCs are the most ancient of our five photoreceptors (Davies, Hankins, & Foster, 2010), and if light-induced pain evolved to discourage looking at the sun (Fishman, 2017), then the connection between the PBR and photophobia could be a very old one. ...
... It is important to note that photophobia is not a disease; rather it is a symptom in association with a disorder. The disorders and conditions associated with photophobia fall into four general categories (Albilali & Dilli, 2018;Digre & Brennan, 2012;Katz & Digre, 2016;Kooij & Bijlenga, 2014;Wu & Hallett, 2017): ...
... Dry eye is a multifactorial ocular surface disease [8]. Montes et al. indicted that patients with dry eye have unstable tear films and irregular corneal surfaces, which significantly increase optical aberration [9] and reduce the retinal imaging quality, further inducing glare disabilities, photophobia [10][11][12][13], and contrast sensitivity(CS) degeneration [14]. Rolando et al. found that the CS of dry eye patients is 35% to 70% lower than that of subjects with normal eyes [15,16]. ...
... Activated stimulation of intrinsically photosensitive retinal ganglion cells has been shown to reduce the uncomfortable symptoms of anti-glare and also improve contrast quality [18]. Filtering out 480 nm or 620 nm light beams showed initial anecdotal efficacy in patients with dry eye or any syndromes which were similar to dry eye patients, such as photosensitive epilepsy, post-traumatic photosensitivity, or eye strain [10]. However, the FL-41 lens that also filters out the 480 nm band does not achieve the same effect, indicating that the manufacturing process of the lens still affects the results of the dependent term. ...
Article
Full-text available
Purpose Glare visual acuity and contrast sensitivity are important indicators of visual quality. Studies have shown that the glare visual acuity and contrast sensitivity in dry eye patients tend to degenerate, further affecting their quality of life. The objective of this study was to investigate the effect of notch filters on glare VA and contrast sensitivity in patients with dry eye or with dry eye syndrome. Method 36 subjects in the 20‒65 age group were diagnosed as having dry eye disease or perceived dry eye syndromes themselves who were included after the initial screening with the OSDI questionnaire, and one was subsequently excluded as they had undergone retinal detachment surgery. Finally, 35 subjects (14 male and 21 female) with a mean age of 40.66 ± 15.62 years participated in this study. All subjects wore their habitual prescriptions and four different filter lenses (namely 480, 620, dual 480 & 620 notch filter, and FL-41 tinted lens), and measured the parameters of glare visual acuity and contrast sensitivity using CSV-1000 and sine wave contrast test (SWCT), respectively. Student t-test and Repeated measurement analysis (R-ANOVA) were utilized by using SPSS 26.0 software. Results A dual-wavelength 480 & 620 nm optical notch filter had a significant anti-glare effect decreasing glare disabilities or discomfort, and leading to better visual quality, the same effect was also shown on a 480 nm notch filter lens. All participants showed a significant difference among the baseline, three notch filters (480 nm, 620 nm, dual-wavelength 480 & 620 nm), and FL-41 tinted lens were used on SWCT_A (1.5 cpd, F = 3.054, p = 0.019) and SWCT_E (18 cpd, F = 2.840, p = 0.049); but did not show statistical different on SWCT_B (3 cpd, F = 0.333, p = 0.771), SWCT_C (6 cpd, F = 1.779, p = 0.159), and SWCT_D (12 cpd, F = 1.447, p = 0.228). The baseline showed the best visual performance on CS at a low spatial frequency (SWCT_A, 1.5 cpd), any filter might reduce the contrast sensitivity at low spatial frequencies in the clinical trial, whereas 480 nm notch filter showed the best effectiveness on CS at a high spatial frequency (SWCT_E, 18 cpd), the FL-41 lens that also filters out the 480 nm band does not achieve the same effect. Moreover, patients with dry eye or those older than 40 years old preferred optical multilayer notch filters to FL-41 tinted lenses. Conclusion The 480- & 620-nm dual-wavelength and 480-nm single-wavelength notch filters have the best effect on the glare visual acuity and contrast sensitivity (CS) at high spatial frequencies in dry eye patients. The 620-nm notch filter performs better in CS at low and mid-low spatial frequencies; the FL-41 tinted lens performs poorly for glare VA and CS spatial frequencies examination. Patients with glare disabilities or CS disturbance at high spatial frequencies may choose a 480-nm notch filter lens, and patients who have CS disturbance at low spatial frequencies may consider a 620-nm notch filter for the prescription.
... Photophobia is the abnormal sensitivity to light and majorly affect patients with more cone cells [2]. The symptom of photophobia presents in two forms, that is the ocular and the central type which is majorly associated with blepharospasm and migraines [3]. However, for ocular presentation, the patients will always complain of intolerance to light both the artificial and the natural light. ...
... The threshold for light sensitivity varies among patients and those with migraines do experience a lower threshold as opposed to those with dry eye and corneal neuropathy [3]. At the same time, the state of retinal adaptation will dictate an individual sensitivity to light. ...
Article
Aim: To assess the implication of tinted Plano lenses in photophobia management. Methods: This was a cross-sectional study among eye care providers in Kenya in which data was collected through online surveys. Three main themes were derived from the study; management of the underlying cause, impact of dispensing tinted Plano lenses and addressing astigmatism. Data was analyzed thematically. Results: The response rate was (100%) with almost three quarter of the respondents (70%) working in private setups. Majority of the respondents (80%) agreed that uveitis, cyclitis, iritis, and blepharitis are strongly associated with photophobia (p=0.001). Although most respondents (78%) were dispensing tinted Plano lenses for patients with visual acuity of 6/6, the patients would still come back with similar complains. Only 24% of the respondents agreed that astigmatism was strongly associated with photophobia (p=0.002). Most respondents agreed that if a patient astigmatic status is corrected even with clear lenses then patients will rarely complain of photophobia. This is more cost effective as tinted Plano lenses remain expensive for majority who presents with photophobia. Conclusion: Photophobia is mismanaged and there is a dire need for eye care providers to properly evaluate the cause of photophobia before deciding on a cost effective management plan. Notwithstanding, eye care professionals should correct any slight astigmatism as it is a major problem that is rarely factored in by most eye care professionals but majorly contributes to photophobia.
... The tints may vary depending upon the effect of dystrophy on visual function and the comfort of the patient. [25,26] A study has reported improvement of visual acuity with red-tinted glasses in a patient with cone dystrophy. [26] Michaelides et al. [22] also suggested that tints were more commonly preferred by patients with cone-rod dystrophies. ...
... [25,26] A study has reported improvement of visual acuity with red-tinted glasses in a patient with cone dystrophy. [26] Michaelides et al. [22] also suggested that tints were more commonly preferred by patients with cone-rod dystrophies. In our study, the patients with cone-related dystrophies predominantly benefited from ET-40 dark gray tint, followed by ET-28 brown tint and clip-on filters. ...
Article
Full-text available
Purpose: The aim of this study was to elucidate the type of low vision devices (LVDs) prescribed for patients with cone dystrophy, cone-rod dystrophy, and rod-cone dystrophy and to analyze the visual improvement with the devices. Methods: A retrospective review of 300 electronic medical records of patients with cone dystrophy, cone-rod dystrophy, and rod-cone dystrophy referred to the low vision care (LVC) clinic for the first time between 2014 and 2016 at a tertiary eye care center was done. Collected data included the demographic profile of patients, details of LVDs, and best-corrected vision. Results: Out of 300 patients, 62.6% (n = 188) were male and 37.3% (n = 112) were female. Of the cases, 50% (n = 150) had cone-rod dystrophy, 45% (n = 135) had cone dystrophy, and 5% (n = 15) had rod-cone dystrophy. The most commonly prescribed LVD was SEE-TV binocular telescope (n = 6, 2.0%) for distance and dome magnifier (n = 60, 20%) for near. ET-40 dark grey tint (20.6%) was preferred for managing photophobia. There was a statistically significant difference in both distance and near visual acuities with LVDs (P < 0.05) in all categories, except rod-cone dystrophy. Conclusion: Early diagnosis with appropriate prescription of LVDs including tints helps in achieving good quality of vision in patients with cone-related dystrophies.
... Photophobia is often also referred to as light sensitivity, photosensitivity, and/or light intolerance, and it can be associated with several ophthalmologic and or neurologic conditions, such as dry eye, blepharospasm, migraine, and traumatic brain injury (TBI). 1,2 Photophobia is one of the most common complaints following mild Traumatic Brain Injury (mTBI). [3][4][5][6] In all, 50% of active duty warfighters and 55% of veterans were diagnosed with photophobia following mTBI. ...
Article
Introduction Photophobia is a common visual symptom following mild traumatic brain injury (mTBI), which can adversely affect the military readiness and performance of service members (SMs). We employed the Defense and Veterans Eye Injury and Vision Registry (DVEIVR) to identify and describe a cohort of SMs diagnosed with photophobia post-mTBI. The objective of this study was to characterize comorbid conditions and symptoms in an mTBI cohort with photophobia, to assess their co-occurrence, to describe the persistence of photophobia, and to assess the effectiveness of utilization of currently available International Statistical Classification of Diseases and Related Health Problems (ICD) codes in reporting photophobia in this cohort. Materials and Methods The DVEIVR database was searched to identify a cohort of SMs experiencing photophobia after mTBI. Photophobia and other potentially related conditions and symptoms, both coded and descriptive, which were abstracted directly from the medical records of SMs, were found within DVEIVR. The presence of the conditions and symptoms comorbid with photophobia was characterized on both patient and encounter levels. Analysis of co-occurrence of photophobia with these conditions or symptoms was performed on the encounter level using co-occur package in the statistical program R. Persistence of photophobia up to 1 year since the injury was assessed. The utilization of currently available ICD codes for photophobia was analyzed. Results A total of 639 SMs exhibiting photophobia after mTBI were identified in DVEIVR. Headaches, including migraines, were the most frequently experienced comorbidity affecting 92% of the SMs in the cohort. The second most frequent complaint was dizziness and/or vertigo (53%) followed by nausea (42%), blurry vision (31%), and irritation and discomfort in the eye (17%). In all, 20% of encounters with photophobia had a complaint of headaches, followed by 8.3% of photophobia encounters co-occurring with dizziness and vertigo, 5.7%—with nausea, 4.5%—with blurred vision, and 2.1%—with subjective sensations in the eye. All comorbidities co-occurred with photophobia at probabilities higher than by chance alone. The percentage of mTBI SMs experiencing photophobia declined to 20% at 30 days after the injury, 17% at 3 months, 12% at 6 months, and 7% at 12 months post-injury, respectively. The use of currently available ICD codes for photophobia was very low—only 27.1% of the cohort had at least 1 ICD code recorded in their medical records. Conclusions The results of this study support the idea that there is a strong relationship between photophobia and headache after an mTBI. Additional research is warranted to better understand this relationship and its causes so that clinical management improves. The results of this study show a precipitous decline in the numbers of cases of photophobia after mTBI over the first 30 days and a longer-term persistence up to a year in a minority of cases, which is consistent with other research in this field. Various ICD codes, which are currently used to code for photophobia, along with other vision conditions, were not widely used to document photophobia symptoms. It is important to adopt a dedicated ICD code for photophobia to improve the surveillance, data collection, and analysis of this condition.
... In individuals without OCA, visual photosensitivity serves as a physiological defense mechanism against potentially harmful intense light (e.g., sunlight). While those without OCA general possess high tolerance to bright light, many conditions, including ophthalmic disorders like ocular albinism, can elevate visual photosensitivity, detrimentally affecting one's quality of life (10) . ...
Article
Full-text available
We present a case report detailing the successful phacoemulsification surgery with artificial iris implantation for two individuals with oculocutaneous albinism. These women suffered from cataracts, resulting in reduced visual acuity and heightened photophobia due to iris pigmentary epithelium deficiency. The patients underwent phacoemulsification along with prosthetic artificial iris implantation into the posterior chamber. This intervention resulted in improved visual acuity, reduced photophobia and glare, and an overall enhanced quality of life. Our report highlights two cases of successful phacoemulsification and artificial iris implantation in patients with oculocutaneous albinism and cataracts, leading to improved visual acuity, reduced photophobia, and enhanced quality of life. Notably, there are no prior records in South American literature of cataract surgery combined with artificial iris implantation for oculocutaneous albinism patients up to the time of this publication. Keywords: Cataract extraction; Albinism; oculocutaneous; Lens implantation; intraocular
... However, the involvement of the ipRGC pathway in the transduction of light information into a painful perception has been put forward due to the projection of ipRGCs directly to pain centers in the posterior thalamus (14)(15)(16). This connection may be a significant part of the "photophobia pathway", which could be pathologically increased in neurological conditions (40). The 24-h rhythmicity of discomfort glare reported in this study, could reflect the activity of this circuitry. ...
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Discomfort glare is a common visual sensation, which is generally reported when being exposed to a brighter lit environment. In certain clinical conditions, this sensation is abnormally amplified, and is commonly named photophobia. Despite the frequent appearance of this sensation in everyday life or in pathological conditions, the underlying mechanisms remain poorly understood. We show here, in highly controlled laboratory constant routine conditions, that light-induced discomfort glare is rhythmic over the 24-hour day. We reveal a strong circadian drive, with a sinusoidal rhythmicity, with maximal discomfort glare in the middle of the night and minimal in the afternoon. We also find a modest sleep-related homeostatic drive of visual discomfort, with a linear increase in discomfort glare over 34 hours of prolonged wakefulness. Our study reveals that discomfort glare is primarily driven by the ipRGC pathway, and that mid and/or long wavelengths cones are involved as well. The 6.5-hour phase lag between the rhythms of photoreceptors’ sensitivity, assessed through pupillary light reflex, and of glare discomfort, suggests two independent underlying mechanisms. In conclusion, our findings highlight the need to take time-of-day and biological rhythmicity into account in the evaluation of light-induced discomfort glare. Apprehending these mechanisms may help understand photophobia in clinical populations, such as in migraine patients, and should be taken into account to optimize light quality at home and at the workplace, both for day and night work.
... Dry eye patients commonly complain of tactile symptoms pertaining to pain and discomfort of the eyes; visual symptoms like light sensitivity, glare, and blurry vision are also prominent in dry eye condition [7][8][9][10][11][12][13]. However, it is unclear to what extent various visual symptoms differentiate dry eye from other eye conditions. ...
Article
Full-text available
Background The diagnosis of dry eye and other common ophthalmological conditions can be supported using patient reported symptoms, which is increasingly useful in contexts such as telemedicine. We aim to ascertain visual symptoms that differentiate dry eye from cataract, glaucoma, or glaucoma suspects. Methods Adults with dry eye, glaucoma, cataract, and suspected glaucoma (controls) completed a questionnaire to rate the frequency and severity of 28 visual symptoms. Univariate, followed by multivariable logistic regression with backward stepwise selection (p < 0.05), determined the individual symptoms and set of symptoms best distinguishing dry eye from each of the other conditions. Results Mean age of 353 patients (94 glaucoma suspect controls, 79 glaucoma, 84 cataract, and 96 dry eye) was 64.1 years (SD = 14.1); 67% were female and 68% White. Dry eye patients reported more frequent light sensitivity (OR = 15.0, 95% CI = 6.3–35.7) and spots in vision (OR = 2.8, 95% CI = 1.2–6.3) compared to glaucoma suspect controls. Compared to glaucoma patients, dry eye patients experienced more frequent light sensitivity (OR = 9.2, 95% CI = 2.0–41.7), but less frequent poor peripheral vision (OR = 0.2, 95% CI = 0.06–0.7), difference in vision between eyes (OR = 0.09, 95% CI = 0.01–0.7), and missing patches of vision (OR = 0.06, 95% CI = 0.009–0.3). Compared to cataract patients, dry eye patients reported more frequent spots in vision (OR = 4.5, 95% CI = 1.5–13.4) and vision variability across the week (OR = 4.7, 95% CI = 1.2–17.7) and were less likely to report worsening vision (OR = 0.1, 95% CI = 0.03–0.4) and blindness (OR = 0.1, 95% CI = 0.02–0.8). Conclusion Visual symptoms may serve as a complementary tool to distinguish dry eye from various ocular conditions, though the symptoms that best distinguish dry eye differ across comparisons. Differentiating how patients visually perceive common eye diseases may be used in a variety of clinical settings to rule out specific conditions.
... 5 Photophobia, or evoked pain to light, is a debilitating symptom which can severely impact an individual's ability to carry out activities of daily living, even when wearing dark glasses. 6 This may result in social impairment, unemployment, or school dropout. 7 Given these significant stressors, an understanding of mechanisms that underlie photophobia in individuals with chronic ocular pain is needed to develop new treatments and improve quality of life. ...
... The headache sensation can vary from sharp throbbing to dull. The onset of headaches can be gradual or sudden, and the duration can range from one hour to a day (Katz & Digre, 2016). ...
Article
Full-text available
Good quality sleep is an important element in maintaining individual health and well-being. Even so, some individuals often experience sleep disorders which can have a negative impact on health. One of the health problems that is often associated with sleep disorders is primary headaches, including migraine headaches and tension headaches. This study aims to determine the relationship between sleep quality and primary headache classification. Data collected in this research used a survey method. This research applies an analytical approach with a cross-sectional design, where data collection is only carried out once. Data were collected through questionnaires evaluating sleep quality using the Pittsburgh Sleep Quality Index and Headache Screening Questionnaire, and data were analyzed using the Chi-square test. The population in this study was 189 students using the Simple Random Findings Technique with 100 samples. This study shows a significant correlation between poor sleep quality and the incidence of migraines and tension headaches, with test results showing a P value of 0.001<0.005. There is a correlation between sleep quality and the incidence of migraines and tension headaches.
... Dry eye patients commonly complain of tactile symptoms pertaining to pain and discomfort of the eyes; visual symptoms like light sensitivity, glare, and blurry vision are also prominent in dry eye condition. (7)(8)(9)(10)(11)(12)(13) However, it is unclear to what extent various visual symptoms differentiate dry eye from other eye conditions. Previous studies have shown that dry eye commonly co-exists with cataracts (40-80% of patients scheduled to have cataract surgery) (14) , (15) and glaucoma (20-59% of glaucoma patients). ...
Preprint
Full-text available
Background: The diagnosis of dry eye and other common ophthalmological conditions can be supported using patient reported symptoms, which is increasingly useful in contexts such as telemedicine. We aim to ascertain visual symptoms that differentiate dry eye from cataract, glaucoma, or glaucoma suspects. Methods: Adults with dry eye, glaucoma, cataract, and suspected glaucoma (controls) completed a questionnaire to rate the frequency and severity of 28 visual symptoms. Univariate, followed by multivariable logistic regression with backward stepwise selection (p<0.05), determined the individual symptoms and set of symptoms best distinguishing dry eye from each of the other conditions. Results: Mean age of 353 patients (94 glaucoma suspect controls, 79 glaucoma, 84 cataract, and 96 dry eye) was 64.1 years (SD=14.1); 67% were female and 68% White. Dry eye patients reported more frequent light sensitivity (OR=15.0, 95% CI=6.3-35.7) and spots in vision (OR=2.8, 95% CI=1.2-6.3) compared to glaucoma suspect controls. Compared to glaucoma patients, dry eye patients experienced more frequent light sensitivity (OR=9.2, 95% CI=2.0-41.7), but less frequent poor peripheral vision (OR=0.2, 95% CI=0.06-0.7), difference in vision between eyes (OR=0.09, 95% CI=0.01-0.7), and missing patches of vision (OR=0.06, 95% CI=0.009-0.3). Compared to cataract patients, dry eye patients reported more frequent spots in vision (OR=4.5, 95% CI=1.5-13.4) and vision variability across the week (OR=4.7, 95% CI=1.2-17.7) and were less likely to report worsening vision (OR=0.1, 95% CI=0.03-0.4) and blindness (OR=0.1, 95% CI=0.02-0.8). Conclusion: Dry eye can be distinguished from various ocular conditions using visual symptoms, though the symptoms that best distinguish dry eye differ across comparisons. Differentiating how patients visually perceive common eye diseases may be used in a variety of clinical settings to rule out specific conditions.
... In particular, we would like to propose the concept of "keratoneuropathy" which can be further differentiated into neurotrophic and neuralgic corneal diseases [5,6]. In Table 1, we have provided a list of (chronic) keratoneuropathies along with the hypothetical mechanisms and clinical pictures. ...
Article
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Ocular comfort is maintained by tear film adequacy, stability, and flow. Sjögren's syndrome, meibomian gland dysfunction, and conjunctivochalasis are the respective ocular surface disease prototypes, respectively; and the umbrella expression, dry eye diseases cover them. We introduced an otherwise primary keratoneuropathy as the fourth independent mechanism for ocular discomfort and pain. We differentiated keratoneuropathy into keratoneuralgic and keratoneurotrophic states, as well.
... [29][30][31] A suggested approach to the diagnosis of light sensitivity and photophobia comprises the assessment of ocular and neurologic causes. 32 Treatment options to relieve symptoms include intense treatment of dry eye, coloured tints, and sunglasses outdoors. 32 ...
Article
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Clinical relevance: Vision-related problems can be part of longstanding sequelae after COVID-19 and hamper the return to work and daily activities. Knowledge about symptoms, visual, and oculomotor dysfunctions is however scarce, particularly for non-hospitalised patients. Clinically applicable tools are needed as support in the assessment and determination of intervention needs. Background: The purpose of this study was to evaluate vision-related symptoms, assess visual and oculomotor function, and to test the clinical assessment of saccadic eye movements and sensitivity to visual motion in non-hospitalised post-COVID-19 outpatients. The patients (n = 38) in this observational cohort study were recruited from a post-COVID-19 clinic and had been referred for neurocognitive assessment. Methods: Patients who reported vision-related symptoms reading problems and intolerance to movement in the environment were examined. A structured symptom assessment and a comprehensive vision examination were undertaken, and saccadic eye movements and visual motion sensitivity were assessed. Results: High symptom scores (26-60%) and prevalence of visual function impairments were observed. An increased symptom score when reading was associated with less efficient saccadic eye movement behaviour (p < 0.001) and binocular dysfunction (p = 0.029). Patients with severe symptoms in visually busy places scored significantly higher on the Visual Motion Sensitivity Clinical Test Protocol (p = 0.029). Conclusion: Vision-related symptoms and impairments were prevalent in the study group. The Developmental Eye Movement Test and the Visual Motion Sensitivity Clinical Test Protocol showed promise for clinical assessment of saccadic performance and sensitivity to movement in the environment. Further study will be required to explore the utility of these tools.
... Photophobia, a high sensitivity to light (photosensitivity), is a common sensory disturbance seen in several neurological conditions, especially migraine which is the third most prevalent disease worldwide (1,2). There are ∼70-80% of migraineurs experiencing photophobia (3). ...
Article
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Background Hypersensitivity to light is a common symptom associated with dysfunction of the occipital region. Earlier studies also suggested that clinically significant right-to-left shunt (RLS) could increase occipital cortical excitability associated with the occurrence of migraine. The aim of this study was to investigate the relationship between RLS and photosensitivity. Methods This cross-sectional observational study included the residents aged 18–55 years living in the Mianzhu community between November 2021 and October 2022. Photosensitivity was evaluated using the Photosensitivity Assessment Questionnaire along with baseline clinical data through face-to-face interviews. After the interviews, contrast-transthoracic echocardiography (cTTE) was performed to detect RLS. Inverse probability weighting (IPW) was used to reduce selection bias. Photosensitivity score was compared between individuals with and without significant RLS using multivariable linear regression based on IPW. Results A total of 829 participants containing 759 healthy controls and 70 migraineurs were finally included in the analysis. Multivariable linear regression analysis showed that migraine (β = 0.422; 95% CI: 0.086–0.759; p = 0.014) and clinically significant RLS (β = 1.115; 95% CI: 0.760–1.470; p < 0.001) were related to higher photosensitivity score. Subgroup analysis revealed that clinically significant RLS had a positive effect on hypersensitivity to light in the healthy population (β = 0.763; 95% CI: 0.332–1.195; p < 0.001) or migraineurs (β = 1.459; 95% CI: 0.271–2.647; p = 0.010). There was also a significant interaction between RLS and migraine for the association with photophobia (pinteraction = 0.009). Conclusion RLS is associated with photosensitivity independently and might exacerbate photophobia in migraineurs. Future studies with RLS closure are needed to validate the findings. Trial registration This study was registered at the Chinese Clinical Trial Register, Natural Population Cohort Study of West China Hospital of Sichuan University, ID: ChiCTR1900024623, URL: https://www.chictr.org.cn/showproj.html?proj=40590.
... Colored glasses, on the other hand, add the color of the lenses to all things in the field of view, causing still another level of annoyance. Meanwhile, because patients tend to be dark-adapted and increase their sensitivity to light, wearing dark or colored glasses indoors is strongly discouraged from a therapy standpoint [18]. ...
Preprint
We propose a smart dimming sunglasses system for individuals with photophobia, especially those who are easily irritated by light intensity. The system uses a spatial light modulator (SLM) to selectively filter light entering the eye based on the scene detection of a camera. By controlling the transmittance of each pixel on the SLM using a modulation function, the proposed sunglasses enable an automated non-linear field of view dimming and also flexible light modulation that meets the photophobic user's visual requirements. Meanwhile, an occlusion mask created on the SLM, which possesses low transmittance to block the incoming light rays, appears blurred from the eye since the focal plane is not on the SLM and blocks the light stimulation insufficiently. To solve this problem, the aperture-based expanded mask has been used in past studies, however, the excessive large expansion ratio used in this approach leads to over-blocking (occlusion leak). In this work, we build an optimization model by simulating the defocused occlusion mask and determining the effective contribution of the degraded pixels based on the occlusion efficiency of the pixel transmittance. While the non-processed mask cannot provide sufficient occlusion and the aperture-based expanded mask causes occlusion leak, our optimized mask attenuates the intensely bright areas to a proper brightness without incorrectly attenuating surrounding areas that no need to modulation.
... Individuals have different thresholds for light sensitivity, and it has been found that migraine patients tend to have lower thresholds compared to the general population (28), not only during headaches but also between attacks (29). A "light-pain matrix" (30) has been hypothesized bridging together retinal structures and various brain area found to be involved in the painful sensation of light processing reported as photophobia, such as thalamus, trigeminal nucleus, superior colliculus and the visual cortex (31). Recently, a class of retinal ganglion cells has been discovered and named intrinsically photosensitive retinal ganglion cell (IPRGC), also known as melanopsin cells (32). ...
Article
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Background Calcitonin gene-related peptide (CGRP) plays a pivotal role in migraine physiology, not only regarding migraine pain but also associated symptoms such as photophobia. The aim of the present study was to assess monoclonal antibodies targeting CGRP efficacy not only in terms of headache and migraine frequency and disability but also in reducing ictal photophobia. Material and methods This is a retrospective observational study, conducted at the Headache Center–ASST Spedali Civili Brescia. All patients in monthly treatment with galcanezumab with at least a 6-month follow-up in September 2022 with reported severe photophobia during migraine attacks were included. Data regarding headache frequency, analgesics consumption, and migraine disability were collected quarterly. Moreover, patients were asked the following information regarding photophobia: (1) whether they noticed an improvement in photophobia during migraine attacks since galcanezumab introduction; (2) the degree of photophobia improvement (low, moderate, and high); and (3) timing photophobia improvement. Results Forty-seven patients were enrolled in the present study as they met the inclusion criteria. Seventeen patients had a diagnosis of high-frequency episodic migraine and 30 of chronic migraine. From baseline to T3 and T6, a significant improvement in terms of headache days (19.2 ± 7.6 vs. 8.6 ± 6.8 vs. 7.7 ± 5.7; p < 0.0001), migraine days (10.4 ± 6.7 vs. 2.9 ± 4.3 vs. 3.6 ± 2.8; p < 0.0001), analgesics consumption (25.1 ± 28.2 vs. 7.6 ± 7.5 vs. 7.6 ± 8.1; p < 0.0001), MIDAS score (82.1 ± 48.4 vs. 21.6 ± 17.6 vs. 18.1 ± 20.5; p < 0.0001), and HIT-6 score (66.2 ± 6.2 vs. 57.2 ± 8.6 vs. 56.6 ± 7.6; p < 0.0001) was found. Thirty-two patients (68.1%) reported a significant improvement in ictal photophobia, with over half of the patients reporting it within the first month of treatment. Photophobia improvement was more frequent in patients with episodic migraine (p = 0.02) and triptans responders (p = 0.03). Conclusions The present study confirms previous reports regarding galcanezumab efficacy beyond migraine frequency. In particular, over 60% of patients, in our cohort, documented a significant improvement also in reducing ictal photophobia. This improvement was, in most patients, moderate to high, and within the first 6 months of treatment, regardless of the clinical response on migraine frequency.
... There is evidence that FL-41 tinted lenses can improve photophobia in patients with migraine headache, but prospective data on the effect in patients with TBI-associated photosensitivity do not exist. 43 A prospective study would be needed to address this concern, with controls to avoid a confounding effect from the anticipated benefit from concurrent headache treatment. ...
Article
Optometric visual rehabilitation therapy has been employed for a variety of visual disorders. Descriptively-named entities such as post trauma visual syndrome (PTVS), visual midline shift syndrome (VMSS), and vertical heterophoria syndrome (VHS) are frequently diagnosed by neuro-optometrists and/or behavioral optometrist in patients after stroke or head injury or in the setting of dizziness and/or headache. The scientific underpinnings of these diagnoses and treatments are weak, and published clinical studies comprise case reports and case series without comparison to control populations. Neuro-ophthalmologists are frequently questioned by patients about the utility of such treatment strategies. Many ophthalmologists and neurologists also are involved in the care of patients who carry these diagnoses and undergo these visual therapies. Involved physicians may benefit from guidance about the rationale, evidence, and level of evidence for the efficacy of these therapeutic approaches.
... 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. ...
Article
Full-text available
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.
... 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
Full-text available
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.
Article
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Exposure to bright light can be visually aversive. This study explored the association between light aversion and various facets of impulsivity. A total of 1,245 participants completed the UPPS-Impulsive Behavior Scale to assess five facets of impulsivity. Additionally, participants responded to questions regarding their aversion to light (e.g., how aversive do you find bright light?). Spearman’s correlation coefficients (rho) revealed that individuals who find light physically aversive, or who experience a negative physical response to exposure (e.g., nausea or headache) triggered by bright indoor light or sunlight, tend to act impulsively under extreme negative and positive affect. Individuals who experience a negative physical response to exposure display greater premeditation, indicating a higher likelihood of considering the potential consequences of their actions. Moreover, these individuals score lower on sensation-seeking, suggesting a reduced inclination to seek out thrilling or novel experiences. These results reveal a complex relationship between light aversion and impulsivity, where those who find light aversive tend to be less impulsive in general, but more impulsive under extreme positive or negative affect.
Article
Background This study evaluates the therapeutic efficacy of HAr® (a novel ophthalmic solution containing modified hyaluronic acid covalently linked to riboflavin) compared to hyaluronic acid eye drops in patients with dry eye disease (DED). Methods Sixteen consecutive patients with bilateral medium to severe DED were divided into two groups. Group 1 received HAr® 0.1 % (Ribohyal®), while Group 2 received HA 0.1 % eye drops. Parameters such as Ocular Surface Disease Index (OSDI) score, osmolarity, break-up time (BUT), non-invasive BUT (NIBUT), tear meniscus measurement, Schirmer test, and Oxford Staining were evaluated. This study has been successfully registered on ClinicalTrials.gov public (Identifier NCT06122428) Results The Ribohyal group showed faster improvement in OSDI scores, with a statistically significant difference at 2 h (mean classification difference: −51.75; p = 0.0003). Photophobia significantly reduced at 2 h, 4 weeks, and 8 weeks in the Ribohyal group compared to baseline (p < 0.0001). Osmolarity improved significantly after 8 weeks in both groups (p < 0.0001). Conclusions HAr® 0.1 % (Ribohyal®) effectively reduced DED symptoms and improved photophobia within 2 h of instillation, lasting up to 8 weeks.
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Purpose: The purpose of this study was to perform a retrospective chart review to see if the use of EScoop® lenses improved the referred veterans' contrast acuity and subjective visual discomfort of glare, photophobia, or difficulty with night driving. Methods: We retrospectively reviewed examinations of 23 veterans aged 36 to 91 who chose EScoop ® for their spectacle prescription. The EScoop ® set available in our clinic included two shades, yellow or orange, two center lens thicknesses (LT), 6 or 9 mm, and with or without 4 prism diopters yoked base up (BU) prism. Results: The largest diagnostic group tested was with traumatic brain injury (12 of 23), and they preferred the orange-tinted lens (10 of 12). The orange 9 mm LT with 4 prism diopters BU was the most commonly chosen EScoop® lens overall (5 of 23). Pre and post lens visual acuity testing with Sloan EDTRS LogMAR Low Contrast Chart at 25% contrast was available for 13 of the 23 patients. A small but statistically significant improvement of 0.11 decimal mean acuity (about one-line Snellen) under a low contrast condition was noted while wearing the preferred EScoop ® lenses (Wilcoxon Signed Rank P=0.015). Conclusion: Our retrospective study reviewed visually impaired patients with varied clinical conditions, including traumatic brain injury, age-related macular degeneration, glaucoma, and optic atrophy. Upon informal questioning, the patients reported improvements in glare, photophobia, and night glare symptoms. Objectively, we measured approximately one line of improvement in contrast Snellen acuity, which was statistically significant. Further research is needed to discern the actual effectiveness of this lens.
Article
Full-text available
Purpose: The purpose of this study was to perform a retrospective chart review to see if the use of EScoop® lenses improved the referred veterans' contrast acuity and subjective visual discomfort of glare, photophobia, or difficulty with night driving. Methods: We retrospectively reviewed examinations of 23 veterans aged 36 to 91 who chose EScoop ® for their spectacle prescription. The EScoop ® set available in our clinic included two shades, yellow or orange, two center lens thicknesses (LT), 6 or 9 mm, and with or without 4 prism diopters yoked base up (BU) prism. Results: The largest diagnostic group tested was with traumatic brain injury (12 of 23), and they preferred the orange-tinted lens (10 of 12). The orange 9 mm LT with 4 prism diopters BU was the most commonly chosen EScoop® lens overall (5 of 23). Pre and post lens visual acuity testing with Sloan EDTRS LogMAR Low Contrast Chart at 25% contrast was available for 13 of the 23 patients. A small but statistically significant improvement of 0.11 decimal mean acuity (about one-line Snellen) under a low contrast condition was noted while wearing the preferred EScoop ® lenses (Wilcoxon Signed Rank P=0.015). Conclusion: Our retrospective study reviewed visually impaired patients with varied clinical conditions, including traumatic brain injury, age-related macular degeneration, glaucoma, and optic atrophy. Upon informal questioning, the patients reported improvements in glare, photophobia, and night glare symptoms. Objectively, we measured approximately one line of improvement in contrast Snellen acuity, which was statistically significant. Further research is needed to discern the actual effectiveness of this lens.
Article
Full-text available
Purpose To investigate the tear proteomic and neuromediator profiles, in vivo confocal microscopy (IVCM) imaging features, and clinical manifestations in neuropathic corneal pain (NCP) patients. Design Cross-sectional study. Methods Twenty NCP patients and twenty age-matched controls were recruited. All subjects were evaluated by corneal sensitivity, Schirmer's test, tear break-up time, corneal and ocular surface staining, Ocular Surface Disease Index and Ocular Pain Assessment Survey questionnaires, as well as IVCM examinations for corneal nerves, microneruomas, epithelial and dendritic cells. Tears were collected for neuromediator and proteomic analysis using enzyme-linked immunosorbent assay and data-independent acquisition mass spectrometry. Results Burning and sensitivity to light were the two most common symptoms in NCP. A total of 188 significantly dysregulated proteins, such as elevated metallothionein-2, creatine kinases B-type, vesicle-associated membrane protein 2, neurofilament light polypeptide, and myelin basic protein, were identified in the NCP patients. The top 10 dysregulated biological pathways in NCP include neurotoxicity, axonal signaling, wound healing, neutrophil degradation, apoptosis, thrombin signaling mitochondrial dysfunction, RHOGDI and P70S6K signaling pathways. Compared to controls, the NCP cohort presented with significantly decreased corneal sensitivity (P<0.001), decreased corneal nerve fiber length (P=0.003), corneal nerve fiber density (P=0.006), nerve fiber fractal dimension (P=0.033), as well as increased in corneal nerve fiber width (P=0.002), increased length, total area and perimeter of microneuromas (P<0.001, P<0.001, P=0.019), smaller corneal epithelial size (P=0.017), and higher nerve growth factor level in tears (p=0.006). Conclusions These clinical manifestations, imaging features, and molecular characterizations would contribute to the diagnostics and potential therapeutic targets for NCP.
Article
Aim: The purpose of this study was to comprehensively explore the ocular toxicity associated with chimeric antigen receptor (CAR) T-cell therapy. Materials & methods: Data were assembled from the US FDA's Adverse Event Reporting System (FAERS) database from 2017 to 2023. Information component and reporting odds ratio methods were used for signal detection in total/categorized CAR T-cell therapy. Results: A total of 17 positive signals (preferred term) were detected, yet none of them were documented in the product information. Some adverse events were with death outcomes and overlapped a lot with cytokine-release syndrome. Conclusion: The ocular adverse events associated with CAR-T cell therapy are noteworthy, and it is imperative to maintain increased alertness and institute early intervention strategies.
Chapter
The Visual Snow Syndrome is a neurological condition that causes flickering dots to appear across a person’s entire field of vision. Those who suffer from this syndrome report seeing an unending stream of flickering dots throughout their visual field. Although patients often experience concurrent migraines, Visual Snow Syndrome appears to be a distinct phenomenon from prolonged migraine aura. The cause of this syndrome is not yet fully understood, but it has been linked to various eye and brain dysfunctions. The aim of this work is to make improvements to the environment in which exercises affected by this condition are developed. Currently, the Visual Snow Initiative provides an online platform where it is possible to carry out a 30-day exercise cycle during which patients are shown videos with noise that simulates Visual Snow and only affects certain areas of the visual field. This video noise moves and shifts along the screen occupying different areas of the screen. The video stream is sent from the servers to the users and requires a modern and efficient internet connection. A single video file occupies about 2GB of disk space. Modern codecs that deal with compressing video and encoding it into browser-supported formats have great difficulty encoding a stream where the pixel matrix of the video is in constant motion. The purpose of this work is to reconstruct the noise that is displayed within the video files for the exercises by means of JavaScript algorithms in such a way as to reduce the download required from users to a few kilobytes and to generate client-side the video that will then be used for the exercise.KeywordsAugmented RealityEyes diseaseVisual Snow SyndromeWeb Programming
Article
Approximately 80% of patients with migraine report light sensitivity during attacks and almost half report that following headache, light sensitivity is the most bothersome symptom. Light wavelengths stimulating intrinsically photosensitive retinal ganglion cells (IPRGCs) exacerbate headache-associated light sensitivity; green light is most comfortable. We developed optical tints that block wavelengths exacerbating migraine pain and transmit wavelengths that are most comfortable. We studied patients with migraine to determine if spectacles with these tints ameliorate headache pain and light sensitivity. Randomized participants wore control lenses or lenses blocking light wavelengths that stimulate IPRGCs. Participants applied the lenses at migraine onset and recorded baseline, two- and four-hour headache pain on an 11-point scale. Primary endpoint was pain reduction at two hours following the first severe or very severe headache. Statistical tests used included mixed-effects model analysis, Mann-Whitney test, Cochran-Mantel-Haenszel test, Shapiro-Wilk test, Welch t-test. In 78 subjects, two- and four-hour pain reduction was not significantly different between groups. In post-hoc analyses of headaches with baseline pain scores ≥ 2, a mixed-effects model suggested that IPRGC lenses were associated with clinically and statistically significant reductions in two- and four-hour headache pain. In post-hoc analyses, fewer subjects wearing IPRGC lenses reported two-hour light sensitivity. Preliminary evidence suggests that optical tints engineered to reduce stimulation of IPRGCs may reduce migraine-associated pain and light sensitivity. Trial Registration: This study was registered at ClinicalTrials.gov (NCT04341298).
Article
Significance: Visual snow syndrome is a relatively new medical condition, with presence of visual snow as the primary visual-perceptual symptom. Information from the present study will improve future clinical diagnostic and treatment aspects in this population. Purpose: To determine the historical, diagnostic, and treatment aspects in patients with documented Visual Snow Syndrome /Visual Snow in an academic, optometric setting. Methods: A retrospective analysis was performed in patients (n = 40, ages 12-55 years) with documented Visual Snow Syndrome /Visual Snow examined over a four-year period. Information was collected by a detailed case history and the Visual Snow Syndrome Symptom Survey. Treatment assessment was performed using the Intuitive Colorimeter and a wide selection of chromatic tints assessed under the most provocative/exacerbating and other conditions. Results: Visual snow was typically constant and monochromatic, with it being present on average 6.43 years. Bright and dark surfaces were the most provocative/exacerbating/revealing conditions, along with the viewing of computer screens. The most common etiology was mild traumatic brain injury. The most common primary and secondary symptoms were photosensitivity and tinnitus, respectively. There was a high frequency of occurrence of oculomotor deficits, especially accommodative and vergence insufficiency (~40-50%). Eighty percent of the patients were prescribed a chromatic tint with subjective visual reduction of VS ranging from 15-100% (mean of 45%). Conclusions: The present information will help in understanding this unusual medico-perceptual condition, especially with respect to simple treatment frequently using readily available chromatic tints.
Article
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Introduction: Light induced amaurosis refers to a transient monocular or binocular vision loss triggered by bright lights. Like amaurosis fugax, light induced amaurosis is associated with carotid artery stenosis but they differ from each other in presentation and pathophysiology. It is thought to be an impairment in the regeneration of retinal visual pigments caused by the inability of carotid circulation to sustain the increased metabolic activity occurring when the retina is exposed to bright lights. With this report we aim to present a case of light induced amaurosis and its management. Case report: We describe a 74-year-old man with the isolated complaint of monocular visual loss from his left eye when exposed to bright lights. These episodes were self-limited and lasted for several minutes. His vision was reportedly good between episodes. He also complained of headache and dizziness. There were no other focal neurological deficits present. The patient had a history of peripheral artery disease, chronic heart failure, hypertension, dyslipidaemia, permanent atrial fibrillation and had a history of heavy smoking in the past. Chronic medical therapy included anticoagulation with rivaroxaban, antiplatelet therapy with acetylsalicylic acid and atorvastatin. Imaging studies (doppler ultrasonography and Computed tomography angiography) revealed a significant morphologic stenosis of the left common carotid artery, left internal carotid artery with sub occlusive disease and right internal carotid artery with 70-75% stenosis (North American Symptomatic Carotid Endarterectomy Trial - NASCET). The vertebral arteries study did not reveal significant morphologic disease. The patient was submitted to left common and internal carotid artery endarterectomy and Dacron patch angioplasty. The visual symptoms progressively improved after surgical treatment. The dizziness and headache were completely gone. Conclusion: Light induced amaurosis is a rare and less known symptom associated with severe carotid artery stenosis. Its timely recognition is important to not deprive patients of timely treatment.
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Çağımızın modern insanı, alışveriş merkezlerinden sinema salonlarına; araç farlarından bilgisayar ekranlarına kadar yaşamın farklı alanında ışığa maruz kalmaktadır. Ayrıca su, kum, kar, asfalt yol ve diğer yansıtıcı yüzeylerden yansıyan ışık, gözleri yormakta ve ışık hassasiyeti (fotofobi) olan kişilerin yaşam kalitesini düşürmektedir. Işığa duyarlılıkla ilgili yapılan küresel bir ankette, Türkiye’de yanıt verenlerin %91’ i ışıktan rahatsız olduğunu belirtmiştir. Pandemi sürecinin hayatımızda meydana getirdiği değişikliklerin bu çalışmaya ilham olduğu söylenebilir. Günümüzde herhangi bir sağlık sebebi ya da çevresel faktörlerden dolayı ışık hassasiyeti olan kişiler için 450 nanometreye(nm) kadar koruma sağlayabilen güneş gözlükleri, 500 nm’ye kadar koruma sağlayabilen sarı kromoforlu yani mavi filtreli lensler bulunmaktadır. Çalışmanın amacı, bu tür ürünlerin ışık blokajının 400-700 nm görünür ışığın üst sınırı olan 700 nm dalga boyuna kadar çıkarılarak geliştirilmesi hakkında alanyazın taraması yaparak kişiler üzerindeki faydasına dikkat çekmektir. Ayrıca mevcut ürünlerin ışık hassasiyeti olan kişilerde tek başına ve 400-700 nm dalga boyundaki görünür ışığa karşı maksimum koruma sağlayamadığından bu konuda ne tür sorunlar yaşanabileceği nitel yöntemin yarı yapılandırılmış görüşme tekniği kullanılarak tespit edilmeye çalışılmıştır. Bu bağlamda yedi soru hazırlanmış hem göz doktorlarıyla hem de optik çalışanlarıyla iletişime geçilerek veriler toplanmıştır. Araştırma verilerinden, mevcut ürünlerin geliştirilmesinin mümkün olduğu, 700 nm’ye kadar tüm zararlı ışıkları bloke edebilecek tek bir optik lens, kozmetik amaçlı renkli lens veya blokajı sağlayacak lens malzemesi üretiminin yapılabileceği bulgulanmıştır. Söz konusu araştırma ile bu tarz ürünlerin geliştirilebilmesine katkı sağlayacak bir alt yapı çalışması oluşturmak ve günümüz insanlarının yeni normalde yaşadığı örtük soruna dikkat çekmek amaçlanmıştır .
Article
Traumatic brain injury disrupts the complex anatomy of the afferent and efferent visual pathways. Injury to the afferent pathway can result in vision loss, visual field deficits, and photophobia. Injury to the efferent pathway primarily causes eye movement abnormalities resulting in ocular misalignment and double vision. Injury to both the afferent and efferent systems can result in significant visual disability.
Article
Photophobia (fear of light) occurs in a wide range of ophthalmic, neurological and behavioural conditions, the most common of which is migraine. The visual discomfort associated with migraine can occur not only in response to bright light but also flicker, spatial pattern and colour. The principles that underlie the discomfort are explored and methods to reduce it are proposed.
Article
Objectives/background: Treatment of migraine in the setting of either renal or hepatic disease can be daunting for clinicians. Not only does the method of metabolism have to be considered, but also the method of elimination/excretion of the parent drug and any active or toxic metabolites. Furthermore, it is difficult to think about liver or kidney disease in isolation, as liver disease can sometimes contribute to impaired renal function and renal disease can sometimes impair hepatic metabolism, through the cytochrome P450 system. Methods: A detailed search for terms related to liver disease, renal disease, and migraine management was performed in PubMed, Ovid Medline, Embase, and the Cochrane Library.For each medication, product labels were retrieved and reviewed using the US FDA website, with additional review of IBM Micromedex, LiverTox, and the Renal Drug Handbook. Results: This manuscript provides an overview of migraine drug metabolism and how it can be affected by liver and renal impairment. It reviews the standard terminology recommended by the US Food and Drug Administration for the different stages of hepatic and renal failure. The available evidence regarding the use of abortive and preventative medicines in the setting of organ failure is discussed in detail, including more recent therapies such as lasmiditan, gepants, and calcitonin gene-related peptide antibodies. Conclusions: For acute therapy, the use of NSAIDS should be limited, as these carry risk for both severe hepatic and renal disease. Triptans can be selectively used, often with dose guideline adjustments. Ubrogepant may be used in severe hepatic disease with dose adjustment and lasmiditan can be used in end stage renal disease. Though non-medicine strategies may be the most reasonable initial approach, many preventative medications can be used in the setting of hepatic and renal disease, often with dose adjustment. This review provides tables of guidelines, including reduced dosing recommendations, for the use of abortive and preventative migraine medications in hepatic and renal failure.
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: 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
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.
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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.
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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.
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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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Significance Light is a powerful stimulant for human alertness and cognition that can be easily administered to improve performance or counteract the negative impact of sleepiness, even during the day. Here, we show that prior exposure to longer wavelength light (orange), relative to shorter wavelength (blue), enhances the subsequent impact of light on executive brain responses. These findings emphasize the importance of light for human cognitive brain function and constitute compelling evidence in favor of a cognitive role for melanopsin. This recently discovered photopigment may therefore provide a unique form of “photic memory” for human cognition and play a broader role than previously apprehended. Ultimately, these findings support the idea that the integration of light exposure over long periods of time can help optimize 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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A variety of animal species utilize the ultraviolet (UV) component of sunlight as their environmental cues, whereas physiological roles of UV photoreception in mammals, especially in human beings, remain open questions. Here we report that mouse neuropsin (OPN5) encoded by the Opn5 gene exhibited an absorption maximum (λmax) at 380 nm when reconstituted with 11-cis-retinal. Upon UV-light illumination, OPN5 was converted to a blue-absorbing photoproduct (λmax 470 nm), which was stable in the dark and reverted to the UV-absorbing state by the subsequent orange light illumination, indicating its bistable nature. Human OPN5 also had an absorption maximum at 380 nm with spectral properties similar to mouse OPN5, revealing that OPN5 is the first and hitherto unknown human opsin with peak sensitivity in the UV region. OPN5 was capable of activating heterotrimeric G protein Gi in a UV-dependent manner. Immuno-blotting analyses of mouse tissue extracts identified the retina, the brain and, unexpectedly, the outer ears as the major sites of OPN5 expression. In the tissue sections of mice, OPN5 immuno-reactivities were detected in a subset of non-rod/non-cone retinal neurons as well as in the epidermal and muscle cells of the outer ears. Most of these OPN5-immuno-reactivities in mice were co-localized with positive signals for the alpha-subunit of Gi. These results demonstrate the first example of UV photoreceptor in human beings and strongly suggest that OPN5 triggers a UV-sensitive Gi-mediated signaling pathway in the mammalian tissues.
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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)wasmorethan6010,000) 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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Background 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. Methods For this case–control study, we recruited chronic migraine patients and compared them with a sex‐ and age‐similar group of control subjects. Patients with peripheral neuropathy, a disease known to be associated with a peripheral neuropathy, or prior corneal or intraocular surgery were excluded. Participants underwent in vivo corneal confocal microscopy using a H eidelberg R etinal T omography III confocal microscope with a R ostock C ornea M odule. Nerve fiber length, nerve branch density, nerve fiber density, and tortuosity coefficient were measured using established methodologies. Migraine participants underwent testing of basal tear production with proparacaine, corneal sensitivity assessment with a cotton‐tip applicator, measurement of tear break‐up time, and completion of a validated dry eye questionnaire. Results A total of 19 chronic migraine patients and 30 control participants completed the study. There were no significant differences in age or sex. Nerve fiber density was significantly lower in migraine patients compared with controls (48.4 ± 23.5 vs 71.0 ± 15.0 fibers/mm ² , P < .001). Nerve fiber length was decreased in the chronic migraine group compared with the control group, but this difference was not statistically significant (21.5 ± 11.8 vs 26.8 ± 5.9 mm/mm ² , P < .084). Nerve branch density was similar in the two groups (114.0 ± 92.4 vs 118.1 ± 55.9 branches/mm ² , P < .864). Tortuosity coefficient and log tortuosity coefficient also were similar in the chronic migraine and control groups. All migraine subjects had symptoms consistent with a diagnosis of dry eye syndrome. Conclusions We found that in the sample used in this study, the presence of structural changes in nociceptive corneal axons lends further support to the hypothesis that the trigeminal system plays a critical role in the pathogenesis of migraine. In vivo corneal confocal microscopy holds promise as a biomarker for future migraine research as well as for studies examining alterations of corneal innervation. Dry eye symptoms appear to be extremely prevalent in this population. The interrelationships between migraine, corneal nerve architecture, and dry eye will be the subject of future investigations.
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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.
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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 (<10000)wasmorethan6010 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)
Article
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.
Article
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.
Article
The purpose of this study was to investigate the long-term visual dysfunction in patients after blast-induced mild traumatic brain injury (mbTBI) using a retrospective case series of 31 patients with mbTBI (>12 mo prior) without eye injuries. Time since mbTBI was 50.5 +/- 19.8 mo. Age at the time of injury was 30.0 +/- 8.3 yr. Mean corrected visual acuity was 20/20. Of the patients, 71% (n = 22) experienced loss of consciousness; 68% (n = 15) of patients in this subgroup were dismounted during the blast injury. Overall, 68% (n = 21) of patients had visual complaints. The most common complaints were photophobia (55%) and difficulty with reading (32%). Of all patients, 25% were diagnosed with convergence insufficiency and 23% had accommodative insufficiency. Patients with more than one mbTBI had a higher rate of visual complaints (87.5%). Asymptomatic patients had a significantly longer time (62.5 +/- 6.2 mo) since the mbTBI than symptomatic patients (42.0 +/- 16.4 mo, p < 0.004). Long-term visual dysfunction after mbTBI is common even years after injury despite excellent distance visual acuity and is more frequent if more than one incidence of mbTBI occurred. We recommend obtaining a careful medical history, evaluation of symptoms, and binocular vision assessment during routine eye examinations in this prepresbyopic patient population.
Article
Photophobia refers to a sensory disturbance provoked by light. However, because it arises distinctly in a broad range of clinical conditions, its definition remains elusive. Many underscore the painful sensory aspects of photophobia, while others emphasize its unpleasant, affective qualities. To add further complexity, recent discoveries in photophobia research have raised disparate and potentially conflicting results. In this installment of an occasional series, we asked clinicians and scientists to give their interpretation of what these discoveries tell us about photophobia in the clinic, and vice versa.
Article
The cornea receives the densest sensory innervation of the body, which is exclusively from small-fiber nociceptive (pain-sensing) neurons. These are similar to those in the skin of the legs, the standard location for neurodiagnostic skin biopsies used to diagnose small-fiber peripheral polyneuropathies. Many cancer chemotherapy agents cause dose-related, therapy-limiting, sensory-predominant polyneuropathy. Because corneal innervation can be detected noninvasively, it is a potential surrogate biomarker for skin biopsy measurements. Therefore, we compared hindpaw-skin and cornea innervation in mice treated with neurotoxic chemotherapy. Paclitaxel (0, 5, 10, or 20mg/kg) was administered to C57/Bl6 mice and peri-mortem cornea and skin biopsies were immunolabeled to reveal and permit quantitation of innervation. Both tissues demonstrated dose-dependent, highly correlated (r = 0.66) nerve fiber damage. These findings suggest that the quantification of corneal nerves may provide a useful surrogate marker for skin peripheral innervation.
Article
Although a universally accepted definition is lacking, mild traumatic brain injury and concussion are classified by transient loss of consciousness, amnesia, altered mental status, a Glasgow Coma Score of 13 to 15, and focal neurologic deficits following an acute closed head injury. Most patients recover quickly, with a predictable clinical course of recovery within the first one to two weeks following traumatic brain injury. Persistent physical, cognitive, or behavioral postconcussive symptoms may be noted in 5 to 20 percent of persons who have mild traumatic brain injury. Physical symptoms include headaches, dizziness, and nausea, and changes in coordination, balance, appetite, sleep, vision, and hearing. Cognitive and behavioral symptoms include fatigue, anxiety, depression, and irritability, and problems with memory, concentration and decision making. Women, older adults, less educated persons, and those with a previous mental health diagnosis are more likely to have persistent symptoms. The diagnostic workup for subacute to chronic mild traumatic brain injury focuses on the history and physical examination, with continuing observation for the development of red flags such as the progression of physical, cognitive, and behavioral symptoms, seizure, progressive vomiting, and altered mental status. Early patient and family education should include information on diagnosis and prognosis, symptoms, and further injury prevention. Symptom-specific treatment, gradual return to activity, and multidisciplinary coordination of care lead to the best outcomes. Psychiatric and medical comorbidities, psychosocial issues, and legal or compensatory incentives should be explored in patients resistant to treatment.
Article
Photoallodynia (photophobia) occurs when normal levels of light cause pain ranging from uncomfortable to debilitating. The only current treatment for photoallodynia is light avoidance. The first step to understanding the mechanisms of photoallodynia is to develop reliable animal behavioral tests of light aversion and identify the photoreceptors required to initiate this response. A reliable light/dark box behavioral assay was developed that measures light aversion independently from anxiety, allowing direct testing of one endophenotype of photoallodynia in mice. Mice lacking intrinsically photosensitive retinal ganglion cells (ipRGCs) exhibit reduced aversion to bright light, suggesting these cells are the primary circuit for light aversion. Mice treated with exogenous μ opiate receptor agonists exhibited dramatically enhanced light aversion, which was not dependent on ipRGCs, suggesting an alternative pathway for light is engaged. Morphine enhances retinal electrophysiological responses to light but only at low levels. This suggests that for the dramatic light aversion observed, opiates also sensitize central brain regions of photoallodynia. Taken together, our results suggest that light aversion has at least two dissociable mechanisms by which light causes specific allodynia behaviors: a primary ipRGC-based circuit, and a secondary ipRGC-independent circuit that is unmasked by morphine sensitization. These models will be useful in delineating upstream light sensory pathways and downstream avoidance pathways that apply to photoallodynia.
Article
SYNOPSIS 20 children with clinically diagnosed migraine were asked to wear either a rose coloured tint or density matched blue tint for a period of 4 months. The frequency, duration and intensity of migraine attacks were recorded, together with the amount of visually provoked beta activity in the EEG. After one month's wear all the children in the study revealed an initial improvement in headache frequency. However, only those children wearing rose tints sustained this improvement up to 4 months, when the mean headache frequency had improved from 6.2 per month to 1.6 per month. The headache frequency of those children wearing blue tints revealed no overall improvement after 4 months. The improvements in headache frequency in children wearing rose tints correlated with a reduction in visually provoked bets activity. Key words: children, migraine, photophobia, tint, visual evoked responses
Article
Photophobia is a common yet debilitating symptom seen in many ophthalmic and neurologic disorders. Despite its prevalence, it is poorly understood and difficult to treat. However, the past few years have seen significant advances in our understanding of this symptom. We review the clinical characteristics and disorders associated with photophobia, discuss the anatomy and physiology of this phenomenon, and conclude with a practical approach to diagnosis and treatment.
Article
To describe the cause and consequence of tear dysfunction-related corneal disease. Perspective on effects of tear dysfunction on the cornea. Evidence is presented on the effects of tear dysfunction on corneal morphology, function, and health, as well as efficacy of therapies for tear dysfunction-related corneal disease. Tear dysfunction is a prevalent eye disease and the most frequent cause for superficial corneal epithelial disease that results in corneal barrier disruption, an irregular optical surface, light scattering, optical aberrations, and exposure and sensitization of pain-sensing nerve endings (nociceptors). Tear dysfunction-related corneal disease causes irritation and visual symptoms such as photophobia and blurred and fluctuating vision that may decrease quality of life. Dysfunction of 1 or more components of the lacrimal functional unit results in changes in tear composition, including elevated osmolarity and increased concentrations of matrix metalloproteinases, inflammatory cytokines, and chemokines. These tear compositional changes promote disruption of tight junctions, alter differentiation, and accelerate death of corneal epithelial cells. Corneal epithelial disease resulting from tear dysfunction causes eye irritation and decreases visual function. Clinical and basic research has improved understanding of the pathogenesis of tear dysfunction-related corneal epithelial disease, as well as treatment outcomes.
Article
The authors investigated whether trigeminal sensitization occurs in response to bright light with the retina disconnected from the rest of the central nervous system by optic nerve section. In urethane-anesthetized rats, trigeminal reflex blinks were evoked with air puff stimuli directed at the cornea in darkness and at three different light intensities. After normative data were collected, the optic nerve was lesioned and the rats were retested. In an alert rat, reflex blinks were evoked by stimulation of the supraorbital branch of the trigeminal nerve in the dark and in the light. A 9.1 × 10(3) μW/cm(2) and a 15.1 × 10(3) μW/cm(2) light significantly enhanced the magnitude of reflex blinks relative to blinks evoked by the same trigeminal stimulus when the rats were in the dark. In addition, rats exhibited a significant increase in spontaneous blinking in the light relative to the blink rate in darkness. After lesioning of the optic nerve, the 15.1 × 10(3) μW/cm(2) light still significantly increased the magnitude of trigeminal reflex blinks. Bright lights increase trigeminal reflex blink amplitude and the rate of spontaneous blinking in rodents. Light can modify trigeminal activity without involving the central visual system.
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