Quantitative Assessment of Subjective Symptoms and Corneal Sensitivity in Chronic Orbital Pain Patients.

PURPOSE: To objectively evaluate the subjective symptoms and characteristics of chronic orbital pain as well as to quantify sensitization of peripheral trigeminal nerves. METHODS: In this prospective cohort study, patients who previously showed a response to peripheral trigeminal nerve blocks for unilateral, idiopathic chronic orbital pain and healthy subjects completed validated questionnaires assessing headaches, neuropathic signs and symptoms, photophobia, and pain qualities. Corneal sensitivity was measured in both eyes for all subjects with a Cochet-Bonnet aesthesiometer. For pain patients, the full assessment protocol was repeated 2-4 weeks after the study injection, and corneal sensitivity was also measured 30 minutes postinjection. Outcomes assessed were headache, neuropathic pain, and photophobia scores; pain qualities; and corneal sensitivity. RESULTS: Six female chronic orbital pain patients (mean age 48.2 years) and 11 female controls (mean age 47.5) were included. The mean headache, neuropathic pain, and photophobia questionnaire scores were significantly higher for pain patients than for controls (p < 0.001). On sensory testing, 5 pain patients (83.3%) endorsed allodynia, and all 6 (100%) had hyperalgesia in the ipsilateral frontal nerve dermatome. No controls had allodynia or hyperalgesia. Corneal sensitivity was similar between eyes in pain patients and between groups. Questionnaire scores and corneal sensitivity did not change significantly after the injection. CONCLUSIONS: Chronic orbital pain patients have a measurable reduction in quality of life due to headaches and photophobia. The supraorbital and supratrochlear nerves are sensitized, resulting in cutaneous hypersensitivity in the corresponding dermatome, but corneal nerves have normal sensitivity.

Validation of the Utah Photophobia Symptom Impact Scale (version 2) as a headache-specific photophobia assessment tool.

OBJECTIVE: To present an updated version of the Utah Photophobia Symptom Impact Scale version 2 (UPSIS2), providing robust clinical and psychometric validation, to improve headache-specific evaluation of light sensitivity and headache-related photophobia. BACKGROUND: The original UPSIS filled a gap in available tools for assessment of headache-associated light sensitivity by providing patient-reported evaluation of the impact of light sensitivity on activities of daily living (ADLs). We have since revised the original questionnaire to provide a more robust item construct and refined validation approach. METHODS: We conducted a psychometric validation of the UPSIS2 through a primary analysis of an online survey of volunteers with recurrent headaches recruited from the University of Utah clinics and surrounding community. Volunteers completed the original UPSIS and UPSIS2 questionnaire versions in addition to measures of headache impact, disability, and frequency. The UPSIS2 now includes a pre-defined recall period and a 1-4 Likert scale with standardized response anchors to improve clarity. Internal construct validity, external construct validity, and test-retest reliability, were evaluated. RESULTS: Responses were obtained from 163 volunteers, with UPSIS2 scores ranging from 15 to 57 (out of a possible 15-60) with a mean (standard deviation) of 32.4 (8.80). Construct validity was satisfactory, as evidenced by sufficient unidimensionality, monotonicity, and local independence. Reliability was excellent, with Rasch test reliability = 0.90 and Cronbach's alpha = 0.92, and an intraclass correlation of 0.79 (95% confidence interval 0.65-0.88) for participants who took the test twice. UPSIS2 correlates well with other headache measures (Spearman's correlations >0.50), as well as the original UPSIS (Spearman's correlation = 0.87), indicating good convergent validity. UPSIS2 scores differ significantly across International Classification of Headache Disorders (third edition) groups, indicating good known group validity. CONCLUSION: The UPSIS2 provides a well-validated headache-specific outcome measure for the assessment of photophobia impact on ADLs.

[Expert consensus on the medical quality evaluation and improvement suggestions of in patients with chronic migraine].

Migraine is a highly disabling primary headache disease, accompanied by nausea, emesis, photophobia and phonophobia. Chronic migraine is usually developed from episodic migraine, and usually comorbids with anxiety, depression, and sleep disorders, further aggravating the disease burden. At present, the clinical diagnosis and treatment of migraine in China are not standard, and the migraine medical quality control evaluation system is lacking. In order to achieve standardized diagnosis and treatment of migraine, headache collaborators of Chinese Society of Neurology, based on national and international clinical research on diagnosis and treatment of migraine and combined with the current situation of China's medical system, drafted the expert consensus on the medical quality evaluation of inpatients with chronic migraine.

Most bothersome symptoms in patients with migraine: A hospital-based study in Taiwan.

OBJECTIVE: To investigate the distribution, clinical associations, and treatment responses for the most bothersome symptoms of migraine in a large sample of patients with migraine in Taiwan. BACKGROUND: The most bothersome symptom is recently recommended as a co-primary endpoint in clinical trials of acute treatment of migraine. However, most clinical trials and observational studies have been conducted in the United States and Europe, with photophobia representing the most common most bothersome symptom. METHODS: Patients who were newly diagnosed with migraine by headache specialists in Taipei Veterans General Hospital were recruited. All participants completed a questionnaire for headache profile, including the most bothersome symptom. Clinical associations of the most bothersome symptoms and response rates to previous acute treatments were analyzed. RESULTS: Among the recruited 1188 patients with migraine (female 79.4%, mean age 39.0 ± 12.1 years) in this cross-sectional study, nausea (n = 729/1188, 61.4%) was the most common symptom that was most bothersome, followed by phonophobia (n = 280/1188, 23.6%), and photophobia (n = 122/1188, 10.3%). The frequency ranking was the same regardless of sex and age. Compared to migraine without aura, migraine with aura was associated with photophobia (adjusted odds ratio [OR] = 2.97, 95% confidence interval [CI] 1.76-5.0, p < 0.001). Chronic migraine was associated with phonophobia (adjusted OR = 1.51, 95% CI 1.13-2.01, p = 0.005), but there was a lower chance for nausea (adjusted OR = 0.68, 95% CI 0.53-0.88, p = 0.004), as the most bothersome symptom. Patients with different most-bothersome symptoms responded similarly to previous acute treatments, with an overall response rate of 52.2% (n = 550/1053). CONCLUSION: Patients with migraine in Taiwan reported a distinct ranking of the most bothersome symptom. However, the response rates of the most bothersome symptom and headache were similar, which supports the most bothersome symptom as an outcome measure for acute treatment of migraine. Further studies recruiting different populations are required to investigate regional differences in most bothersome symptoms.

Brain trauma impacts retinal processing: photoreceptor pathway interactions in traumatic light sensitivity.

BACKGROUND: Concussion-induced light sensitivity, or traumatic photalgia, is a lifelong debilitating problem for upwards of 50% of mild traumatic brain injury (mTBI) cases, though of unknown etiology. We employed spectral analysis of electroretinographic (ERG) responses to assess retinal changes in mTBI as a function of the degree of photalgia. METHODS: The design was a case-control study of the changes in the ERG waveform as a function of level of light sensitivity in individuals who had suffered incidents of mild traumatic brain injury. The mTBI participants were categorized into non-, mild-, and severe-photalgic groups based on their spectral nociophysical settings. Light-adapted ERG responses were recorded from each eye for 200 ms on-off stimulation of three spectral colors (R:red, G:green, and B:blue) and their sum (W:white) at the highest pain-free intensity level for each participant. The requirement of controls for testing hypersensitive individuals at lower light levels was addressed by recording a full light intensity series in the control group. RESULTS: Both the b-wave and the photopic negative response (PhNR) were significantly reduced in the non-photalgic mTBI group relative to controls. In the photalgic groups, the main b-wave peak shifted to the timing of the rod b-wave, with reduced amplitude at the timing of the cone response. CONCLUSION: These results suggest the interpretation that the primary etiology of the painful light sensitivity in mTBI is release of the rod pathway from cone-mediated inhibition at high light levels, causing overactivation of the rod pathway.

Visual photosensitivity threshold and objective photosensitivity luminance in healthy human eyes assessed using an automated ocular photosensitivity analyser: a step towards translation of a clinical tool for assessing photophobia.

PURPOSE: To evaluate the visual photosensitivity threshold and objective photosensitivity luminance in healthy eyes, thereby providing a normative dataset that will lead to a better understanding of diseases causing photophobia. METHODS: This was a prospective cross-sectional study. Emmetropes whose visual acuity was better than 0.18 logMAR (6/9) with no other ocular abnormality were included. Headache Impact Test-6 and visual light sensitivity questionnaires were administered. Visual photosensitivity threshold was measured subjectively using the ocular photosensitivity analyser. Objective photosensitivity luminance was assessed manually by evaluating videos recorded using an infrared camera and noting the intensity of light at the first squeezing reflex. RESULTS: Seventy five normal subjects (age range, 7-71 years) were included. Median age was 32.7 years (inter-quartile range, 20.3-47.9 years). Forty (53.3%) were males. Median Headache Impact Test score was 38 (inter-quartile range, 36-42) and visual light sensitivity questionnaire score was 11 (inter-quartile range, 8-15). Mean (standard deviation) right eye, left eye and binocular visual photosensitivity threshold was 3.34 (0.78), 3.33 (0.81) and 3.37 (0.78) loglux, respectively. There was a significant negative correlation of visual light sensitivity questionnaire scores with right eye, left eye and binocular visual photosensitivity thresholds, and positive correlation of age with binocular visual photosensitivity thresholds. Mean (standard deviation) right eye, left eye and binocular objective photosensitivity luminance was 3.25 (0.55), 3.35 (0.47) and 3.15 (0.52) loglux, respectively. Age was only positively correlated with binocular objective photosensitivity luminance, and there was no correlation between age and right eye or left eye objective photosensitivity luminance. CONCLUSIONS: The study characterised, for the first time, objective photosensitivity luminance and established normative data for both visual photosensitivity threshold and objective photosensitivity luminance. The data will help in understanding the pathophysiology of diseases causing photophobia, monitoring the disease progression and evaluating treatment modalities.

The Unmet Challenge of Diagnosing and Treating Photophobia.

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.

Photophobia as a Presenting Feature in Adie's Tonic Pupil.

A 34 years old female presented with complains of photophobia since 6-7 months. On examination, she had anisocoria of 4 mm in room light which increased in bright light. The left pupil was dilated and unresponsive to direct and indirect light stimuli. It did however, constrict slowly on near fixation followed by slow redilatation on distance fixation. A diagnosis of Adie's tonic pupil was made since left pupil constricted with instillation of dilute pilocarpine 0.1%. Her symptoms of photophobia and blurred vision immediately resolved. Photochromatic glasses and dilute pilocarpine 0.1% three times a day were prescribed. Prompt symptomatic relief of photophobia and blurred vision was observed.

THE LOSS OF INFRARED LIGHT SENSITIVITY OF PHOTORECEPTOR CELLS MEASURED WITH TWO-PHOTON EXCITATION AS AN INDICATOR OF DIABETIC RETINOPATHY: A Pilot Study.

PURPOSE: Human photoreceptors are sensitive to infrared light (IR). This sensitivity can be used as a novel indicator of retinal function. Diabetic retinopathy patients were assessed using in vivo two-photon excitation and compared their scotopic IR threshold with that of healthy patients. METHODS: Sixty-two participants, 28 healthy and 34 with diabetic retinopathy, underwent a comprehensive eye examination, where visual acuity and contrast sensitivity were assessed. Infrared thresholds were measured in the fovea and parafovea following 30-minute dark adaptation. A two-photon excitation device was used with integrated pulsed laser light (1,045 nm) for sensitivity testing and scanning laser ophthalmoscopy for fundus imaging. RESULTS: The mean Snellen visual acuity of diabetic patients (6/7.7) was worse than that of the healthy patients (6/5.5), which was significantly different (P < 0.001). Disease patients had decreased contrast sensitivity, especially at 6 and 18 cycles/degree. The mean retinal sensitivity to IR light in eyes with diabetic retinopathy (11.6 ± 2.0 dB) was significantly (P < 0.001) lower than that in normal eyes (15.5 ± 1.3 dB). CONCLUSION: Compared with healthy control subjects, the IR light sensitivity of diabetic patients was significantly impaired. Two-photon measurements can be used in the assessment of retinal disease, but further studies are needed to validate IR light stimulation in various stages of diabetic retinopathy.

Ichthyosis follicularis, atrichia and photophobia (IFAP) and hereditary mucoepithelial dysplasia: Two syndromes that share a common clinical spectrum.

Ichthyosis follicularis, atrichia and photophobia syndrome (IFAP) is an X-linked inherited disease caused by pathogenic variants in the gene encoding the membrane-bound transcription factor peptidase, site 2 (MBTPS2). Clinical presentation includes ichthyosis follicularis, alopecia, photophobia and developmental delay. Hereditary mucoepithelial dysplasia (HMD) is a dominantly inherited disease characterized by keratitis, non-scarring alopecia, skin lesions including follicular keratosis, perineal erythema, and mucosal involvement. Recently, variants in SREBF1, a gene coding for a transcription factor related to cholesterol and fatty acid synthesis, have been associated with the disease. These two syndromes share a common clinical spectrum. Here, we describe an IFAP syndrome patient with a novel variant in the MBTPS2 gene and an HMD patient with a previously reported variant in the SREBF1 gene. In addition, we present a review of the literature describing the triad characterized by non-scarring alopecia, keratosis follicularis, and ocular symptoms common in both IFAP and HMD patients to raise awareness of these underdiagnosed diseases. We also highlight the subtle differences in clinical presentation between the two disorders to better enable differentiation.

Quantification of photophobia in visual snow syndrome: A case-control study.

OBJECTIVE: To quantify photophobia in visual snow syndrome (VSS), a debilitating migraine-associated visual disturbance manifesting with continuous "TV snow-like" flickering dots in the entire visual field and additional visual symptoms, such as photophobia. METHODS: Photophobia was compared between 19 patients with VSS and 19 controls matched for age, sex, migraine and aura using the Leiden Visual Sensitivity Scale (L-VISS). RESULTS: Patients with VSS had an increased L-VISS-score compared to matched controls [(22.2 ± 5.9 vs. 4.4 ± 4.8; ANOVA, factors VSS and comorbid migraine: Main effect for VSS (F = 100.70; p < 0.001), but not for migraine (F < 0.01; p = 1.00) or the interaction (F = 1.93; p = 0.16)]. An L-VISS-score of 14 identified VSS with a sensitivity and specificity of 95% (Receiver Operating Characteristic analysis, 0.986 ± 0.014, p ≤ 0.001). CONCLUSION: Patients with VSS suffer continuously from photophobia at a level similar to chronic migraineurs during attacks. Although migraine and VSS share dysfunctional visual processing, patients with VSS might be more severely affected.

Most Bothersome Symptom in Persons With Migraine: Results From the Migraine in America Symptoms and Treatment (MAST) Study.

OBJECTIVES: The objectives of this study were to determine the rates of nausea, phonophobia, and photophobia reported overall and as the most bothersome symptom (MBS) in individuals with migraine and to identify individual characteristics associated with each of the 3 candidate MBSs. BACKGROUND: The MBS has emerged as an important coprimary efficacy endpoint in clinical trials of acute treatments for migraine, as recommended by the Food and Drug Administration. The current understanding of how persons with migraine designate an associated symptom as the most bothersome has been assessed primarily in the context of randomized trials. METHODS: Respondents (n = 95,821) in the cross-sectional, observational Migraine in America Symptoms and Treatment (MAST) study were adults (aged ≥18 years) recruited from a US nationwide online research panel. A validated diagnostic screener identified 15,133 individuals who met modified International Classification of Headache Disorders (ICHD)-3 beta criteria for migraine and reported at least 1 monthly headache day (MHD) over the previous 3 months. The survey ascertained sociodemographic variables, headache-related disability, MHDs, cutaneous allodynia, medication overuse, a migraine symptom severity score, pain interference, noncephalic pain, anxiety and depression symptoms, visual aura over the previous year, and acute treatment optimization. The current analysis is based on respondents who also completed a 6-month follow-up assessment that included questions about their most bothersome headache symptom. RESULTS: A total of 7518 respondents completed the 6-month follow-up, and 6045 met inclusion criteria and were included in the analysis. The mean age of respondents was 47 (SD 13.4) years, 76.0% (4596/6045) were women, and 84.8% (5103/6017) were white. Among all respondents, 64.9% reported all 3 migraine symptoms. The MBS was photophobia in 49.1% (2967/6045), nausea in 28.1% (1697/6045), and phonophobia in 22.8% (1381/6045). Respondents reporting photophobia as the MBS were more likely to be men, to be obese, and to report visual aura. Those reporting nausea as the MBS were more likely to be women, to have lower incomes, and to report lower levels of treatment optimization. Respondents reporting phonophobia as the MBS were more likely to have cutaneous allodynia and less likely to have visual aura. CONCLUSION: Most people with migraine in the MAST observational study reported all 3 cardinal symptoms of nausea, photophobia, and phonophobia. As in clinical trials, the most common MBS was photophobia. Patient profiles differed among the groups defined by their MBS.

Validation of a photophobia symptom impact scale.

BACKGROUND: Routine assessment of photophobia in the clinical setting may underestimate the presence and severity of this condition. We aimed to develop and validate a questionnaire to improve evaluation of the impact of photophobia on activities of daily living, and to determine the relationship of this questionnaire to psychophysical assessment of light sensitivity thresholds. METHODS: We developed the 17-item Utah Photophobia Symptom Impact Scale (UPSIS-17) and compared its psychometric properties to the 8-item Korean Photophobia Questionnaire (KUMC-8). Ninety five subjects with or without light sensitivity completed both questionnaires; 72 also completed laboratory-based assessment of light sensitivity thresholds. We used Rasch analysis to evaluate instrument targeting, including internal consistency and reliability. Correlation analysis was used to assess the relationship between questionnaire scores and light sensitivity thresholds. RESULTS: We observed correlation between UPSIS-17 and KUMC-8, r = 0.72 (p < 0.0001). Higher UPSIS-17 scores correlated with light sensitivity thresholds, r = -0.42 (p < 0.0001), whereas KUMC-8 scores did not significantly correlate with light sensitivity thresholds, r = -0.21 (p = 0.072). UPSIS-17 showed better instrument targeting than KUMC-8 on Rasch analysis. Person-item maps allowed for identification of questions that could be removed without affecting questionnaire validity measures. CONCLUSION: This study resulted in a shortened, 12-item questionnaire. The UPSIS-12 retained significant correlation with both the KUMC-8 and light sensitivity thresholds, yielding a simpler tool for symptom assessment, while retaining validity. This expanded tool may be useful in clinical, as well as research settings, for collection of data about disability due to photophobia.

Relating Photophobia, Visual Aura, and Visual Triggers of Headache and Migraine.

OBJECTIVE: This study investigated a potential association between visual factors and symptoms related to migraine. It was predicted that photophobia and visual aura would be positively associated with interictal light sensitivity and visual headache triggers (flicker, glare, and eyestrain), and that these 2 visual symptoms would also be associated. BACKGROUND: Previous studies have found independent neurophysiological associations between several visual factors and symptoms related to headache disorders. Many of these connections appear to be associated with increased cortical hypersensitivity, a phenomenon that might be in part due to repeated avoidance and reduced tolerance to triggers. If true, and if associations between visual factors and symptoms can be established, this may have implications for an exposure-based treatment for migraine symptoms. METHODS: Four hundred and ninety-one participants (411 female, 80 male) were recruited through Griffith University (AUS), Headache Australia, Pain Australia, and through social media. Participants were grouped based on the presence of headache disorder symptoms and the presence or absence of photophobia and/or visual aura. A cross-sectional online survey design was utilized to gather information pertaining to interictal light sensitivity, visual triggers, and visual symptoms. RESULTS: With respect to interictal light sensitivity and photophobia, a significant difference (P < .001, eta squared [η2 ] = 0.084) was found between the 3 groups, where headache disorder participants with photophobia (group A1; mean [M] = 2.5, standard deviation [SD] = 0.97) reported significantly greater light sensitivity than participants with headache disorder and no photophobia (A2; M = 1.68, SD = 0.62) and control group participants (A3; M = 1.82, SD = 0.85). This pattern was repeated for participants reporting flicker as a headache trigger (P < .001, η2 = 0.061), with group A1 (M = 2.45, SD = 1.24) significantly higher than groups A2 (M = 1.68, SD = 0.83) and A3 (M = 1.68, SD = 0.89), and was also seen for glare as a headache trigger (P < .001, η2 = 0.092), with group A1 (M = 2.92, SD = 0.96) significantly higher than A2 (M = 2.31, SD = 0.89) and A3 (M = 2.09, SD = 0.93). This pattern of results was not replicated for headache disorder participants with and without visual aura. A significant association (P < .001) was found between photophobia and visual aura in headache disorder participants based on a chi-square test of independence, with 86/136 participants reporting either both or neither visual symptom. CONCLUSIONS: This study supports a link between certain visual phenomena in headache disorder populations, and supports future research into exposure-based treatments for migraine symptoms.

Two cases of unilateral cone-rod dysfunction with negative electroretinograms.

PURPOSE: To report the findings in two patients with unilateral cone-rod dysfunction with the a-wave larger than the b-wave, i.e., negative-type, full-field electroretinogram (ERG). METHODS: Standard ophthalmological examinations were performed including the medical history, measurements of the best-corrected visual acuity and intraocular pressures, slit-lamp biomicroscopy, ophthalmoscopy, spectral-domain optical coherence tomography, fundus autofluorescence, fluorescein angiography, and perimetry. ERG examinations were carried out with the ISCEV standard. Immunoblot analysis using the patient's sera was performed to determine the presence of the recoverin1 antibody. RESULTS: The common findings in these two patients were: unilateral, male sex, sudden onset of photophobia or a reduction in the vision at an advanced age, preserved visual acuity, no complaint of night blindness, normal fundus appearance, negative-type dark-adapted 3.0 ERGs with reduced a-wave amplitudes, absent light-adapted 3.0 ERGs, and very reduced but recordable dark-adapted 0.01 ERGs. In addition, the multifocal ERGs in all areas except that in a hexagonal area within a 2.5° radius of the fovea were very reduced. Patients with similar findings have been reported earlier, but the subnormal a-wave of the dark-adapted 3.0 ERGs and extensive morphological alterations of the retina in the posterior pole in the OCT images were different from those of the reported patients. The OCT images showed an indistinct interdigitation zone and discontinuous ellipsoid zone. Anti-recoverin antibodies were not detected. CONCLUSIONS: Negative ERGs with severely reduced cone and rod components suggest that both the cone and rod bipolar cell visual pathways may be disturbed. Slightly decreased a-wave suggests minor abnormality of photoreceptors. It is important to determine whether these patients represent a new clinical entity or a phenotypic variation of an already described retinal disorder.

Retinal phenotypic characterization of patients with ABCA4 retinopathydue to the homozygous p.Ala1773Val mutation.

Purpose: To describe the retinal clinical features of a group of Mexican patients with Stargardt disease carrying the uncommon p.Ala1773Val founder mutation in ABCA4. Methods: Ten patients carrying the p.Ala1773Val mutation, nine of them homozygously, were included. Visual function studies included best-corrected visual acuity, electroretinography, Goldmann kinetic visual fields, and full-field electroretinography (ERG). In addition, imaging studies, such as optical coherence tomography (OCT), short-wave autofluorescence imaging, and quantitative analyses of hypofluorescence, were performed in each patient. Results: Best-corrected visual acuities ranged from 20/200 to 4/200. The median age of the patients at diagnosis was 23.3 years. The majority of the patients had photophobia and nyctalopia, and were classified as Fishman stage 4 (widespread choriocapillaris atrophy, resorption of flecks, and greatly reduced ERG amplitudes). An atypical retinal pigmentation pattern was observed in the patients, and the majority showed cone-rod dystrophy on full-field ERG. In vivo retinal microstructure assessment with OCT demonstrated central retinal thinning, variable loss of photoreceptors, and three different patterns of structural retinal degeneration. Two dissimilar patterns of abnormal autofluorescence were observed. No apparent age-related differences in the pattern of retinal degeneration were observed. Conclusions: The results indicate that this particular mutation in ABCA4 is associated with a severe retinal phenotype and thus, could be classified as null. Careful phenotyping of patients carrying specific mutations in ABCA4 is essential to enhance our understanding of disease expression linked to particular mutations and the resulting genotype-phenotype correlations.

Photophobia: When Light Hurts, a Review.

PURPOSE OF REVIEW: To provide an updated overview of Photophobia with a particular focus on photophobia related to migraine. RECENT FINDINGS: Melanopsin-containing photoreceptors called intrinsically photosensitive retinal ganglion cells (ipRGCs) have been identified in the retina and explain the rational for photophobia in individuals who are blind. Photophobia, a sensory disturbance provoked by light, is a common neurological and ophthalmological symptom. Migraine, a common neurological condition, is pathognomonic of photophobia; however, other primary headache conditions, traumatic brain injury, and impairment of the optic pathway can cause photophobia. In addition, anterior and posterior segment ocular pathology, medications, and psychiatric conditions can result in photophobia. At least 2 (possibly three) distinct neural pathways are involved in photophobia. Some of the basic science regarding these pathways is discussed in this review including the role of calcitonin gene-related peptide (CGRP) and pituitary adenylate cyclase-activating polypeptide. Management of photophobia includes treatment of the underlying etiology and conservative strategies such as wearing sunglasses.

Headache attributed to aeroplane travel: the first multicentric survey in a paediatric population affected by primary headaches.

BACKGROUND: This multicentric survey investigates the prevalence and characteristics of Airplane Headache in children affected by primary headaches. METHODS: Patients with symptoms of Airplane Headache were recruited from nine Italian Pediatric Headache Centres. Each patient was handed a structured questionnaire which met the ICHD-III criteria. RESULTS: Among 320 children suffering from primary headaches who had flights during their lifetime, 15 (4.7%) had Airplane Headache, with mean age of 12.4 years. Most of the patients were females (80%). The headache was predominantly bilateral (80%) and localized to the frontal area (60%); it was mainly pulsating, and lasted less than 30 min in all cases. Accompanying symptoms were tearing, photophobia, phonophobia in most of the cases (73.3%). More than 30% of patients used medications to treat the attacks, with good results. CONCLUSION: Our study shows that Airplane Headache is not a rare disorder in children affected by primary headaches and highlights that its features in children are peculiar and differ from those described in adults. In children Airplane Headache prevails in females, is more often bilateral, has frequently accompanying symptoms and occurs at any time during the flight. Further studies are needed to confirm the actual frequency of Airplane Headache in the general pediatric population not selected from specialized Headache Centres, with and without other concomitant headache condition, and to better clarify the clinical characteristics, pathophysiology and potential therapies.

Efficacy and safety of DFN-11 (sumatriptan injection, 3 mg) in adults with episodic migraine: an 8-week open-label extension study.

BACKGROUND: DFN-11, a 3 mg sumatriptan subcutaneous (SC) autoinjector for acute treatment of migraine, has not been assessed previously in multiple attacks. The objective of this study was to evaluate the efficacy, tolerability, and safety of DFN-11 in the acute treatment of multiple migraine attacks. METHODS: This was an 8-week open-label extension of multicenter, randomized, double-blind, placebo-controlled US study. Subjects averaging 2 to 6 episodic migraine attacks per month were randomized to DFN-11 or placebo to treat a single attack of moderate-to-severe intensity and then entered the extension study to assess the efficacy, tolerability, and safety of DFN-11 in multiple attacks of any pain intensity. RESULTS: Overall, 234 subjects enrolled in the open-label period, and 29 (12.4%) discontinued early. A total of 848 migraine episodes were treated with 1042 doses of open-label DFN-11 and subjects treated a mean (SD) of 3.9 (2.3) attacks. At 2 h postdose in attacks 1 (N = 216), 2 (N = 186), 3 (N = 142) and 4 (N = 110), respectively, pain freedom rates were 57.6%, 64.6%, 61.6%, and 66.3%; pain relief rates were 83.4%, 88.4%, 84.1%, and 81.7%; most bothersome symptom (MBS)-free rates were 69.0%, 76.5%, 77.7%, and 74.7%; nausea-free rates were 78.1%, 84.6%, 86.5%, and 85.7%; photophobia-free rates were 75.3%, 76.4%, 72.3%, and 77.5%; and phonophobia-free rates were 75.2%, 77.5%, 73.6%, and 76.0%. Overall, 40.6% (89/219) of subjects reported treatment-emergent adverse events (TEAE), the most common of which were associated with the injection site: swelling (12.8%), pain (11.4%), irritation (6.4%), and bruising (6.4%). Most subjects (65.2%, 58/89) had mild TEAEs; severe TEAEs were reported by 1 subject (treatment-related jaw tightness). Five subjects (2.1%) discontinued due to adverse events, which included mild throat tightness (n = 2), moderate hernia pain (n = 1), moderate hypersensitivity (n = 1), and 1 subject with mild nausea and moderate injection site swelling. There were no serious TEAEs and no new or unexpected safety findings. CONCLUSION: DFN-11 was effective, tolerable, and safe in the acute treatment of 4 migraine attacks over 8 weeks, with consistent responses on pain and associated symptoms. Most TEAEs were mild, with a very low incidence of triptan-related TEAEs. DFN-11 is potentially an effective and safe alternative for the acute treatment of migraine. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02569853 . Registered 07 October 2015.

The role of visual system in migraine.

The visual system is involved in different ways in migraine. Visual auras are the most common form of migraine aura. It may consist of positive or negative visual symptoms and cortical spreading depression is felt to be the phenomenon that underlies it. Even in migraine without aura, vision it is not totally excluded given that one of the major criteria for the diagnosis of migraine is photophobia. In persistent visual aura, patients refer symptoms defined as visual snow and television static. In retinal migraine unilateral decreased vision or complete visual loss occurs. Ophthalmoplegic migraine is characterized by palsy of one among the three ocular motor nerves. Migraine visual aura, particularly when occurring without headache, is a diagnosis of exclusion. Imaging studies and laboratory tests should exclude neurologic disease, included seizures and central nervous system tumor, ocular pathologies, carotid or cardiac disease, thrombosis and connective tissue disease.