Individualized spectral filters alleviate persistent photophobia, headaches and migraines in active duty military and Veterans following brain trauma.

PURPOSE: Consistent with association between photophobia and headache, growing evidence suggests an underlying causal relationship between light sensitivity and central pain. We investigated whether an intervention to regulate light sensitivity by filtering only wavelengths causing difficulties for the specific individual could alleviate headaches/migraines resulting from traumatic brain injury (TBI). METHODS: Secondary data analysis of a clinical database including N = 392 military personnel (97% men, 3% women), ranging in age from 20 to 51 years, diagnosed with TBI, persistent headaches/migraines, and light sensitivity. The average elapsed time from TBI diagnosis to intervention was 3 years. Headache/migraine severity, frequency, medication use, and difficulties related to daily functioning were assessed pre and 4-12 weeks post-intervention with individualized spectral filters. RESULTS: Monthly migraine frequency decreased significantly from an average of 14.8 to 1.9, with 74% reporting no migraines post-intervention. Prescription and over-the-counter medication use decreased by more than 70%. Individuals also reported significant improvement in light sensitivity, headaches/migraine severity, and physical and perceptual symptoms. CONCLUSIONS: Wearing individualized spectral filters was associated with symptom relief, increased subjective quality of reported health and well-being, and decreased objective medication use for TBI-related persistent headaches/migraines. These results support a suggested relationship between dysregulated light sensitivity and central regulation of pain.

Targeting the intrinsically photosensitive retinal ganglion cell to reduce headache pain and light sensitivity in migraine: A randomized double-blind trial.

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).

Gene-independent therapeutic interventions to maintain and restore light sensitivity in degenerating photoreceptors.

Neurodegenerative retinal diseases are a prime cause of blindness in industrialized countries. In many cases, there are no therapeutic treatments, although they are essential to improve patients' quality of life. A set of disease-causing genes, which primarily affect photoreceptors, has already been identified and is of major interest for developing gene therapies. Nevertheless, depending on the nature and the state of the disease, gene-independent strategies are needed. Various strategies to halt disease progression or maintain function of the retina are under research. These therapeutic interventions include neuroprotection, direct reprogramming of affected photoreceptors, the application of non-coding RNAs, the generation of artificial photoreceptors by optogenetics and cell replacement strategies. During recent years, major breakthroughs have been made such as the first optogenetic application to a blind patient whose visual function partially recovered by targeting retinal ganglion cells. Also, RPE cell transplantation therapies are under clinical investigation and show great promise to improve visual function in blind patients. These cells are generated from human stem cells. Similar therapies for replacing photoreceptors are extensively tested in pre-clinical models. This marks just the start of promising new cures taking advantage of developments in the areas of genetic engineering, optogenetics, and stem-cell research. In this review, we present the recent therapeutic advances of gene-independent approaches that are currently under clinical evaluation. Our main focus is on photoreceptors as these sensory cells are highly vulnerable to degenerative diseases, and are crucial for light detection.

Migraine and light: A narrative review.

OBJECTIVE: In this narrative review, we summarize clinical and experimental data on the effect of light in migraine and discuss future prospects. BACKGROUND: Effective nonpharmacological treatment of hypersensitivity to light in migraine is an unmet clinical need. Current management strategies primarily consist of seeking a dark room and avoiding light exposure. Advances in the past 2 decades have improved our understanding of the underlying pathophysiology of how migraine is influenced by light. This may provide promising avenues for novel approaches in clinical management. METHODS: We searched MEDLINE for articles published from database inception up to September 1, 2021. We used the search term "migraine" with the search terms "light," "photophobia," "treatment," "trigger," "circadian rhythm," "environment," and/or "pathophysiology." RESULTS: Light is commonly reported as a trigger factor of migraine attacks, however, early manifestation of photophobia and false attribution is likely the actual cause based on data deriving from retrospective, prospective, and experimental studies. The most common photophobia symptoms in migraine are exacerbation of headache by light and abnormal sensitivity to light with the underlying neural pathways likely being dependent on ongoing activity in the trigeminovascular system. Clinical studies and experimental models have identified mediators of photophobia and uncovered narrow wavebands of the light spectrum that may reduce pain intensity during a migraine attack. Consequently, novel devices have undergone exploratory clinical trials with promising results. CONCLUSION: False attribution is likely the reason why light is commonly reported as a trigger factor of migraine attacks, and a prospective confirmation is required to prevent unnecessary avoidance. The observation that individuals with migraine are not equally photophobic to all wavebands of the light spectrum opens the potential for innovative pain management strategies. In this context, using human-centric lighting (also called integrative lighting) to mimic the natural daylight cycle and avoid harmful wavebands through modern technology may prove beneficial. Future research should identify direct and indirect consequences of light and other environmental factors in migraine to fill out knowledge gaps and enable evidence-based care strategies within institutions, work environments, and other settings.

Piggyback Photochromic Contact Lens for Visual Rehabilitation and Photophobia Management in Traumatic Aniridia.

ABSTRACT: We report herein a case of fitting with a photochromic silicone hydrogel contact lens under a rigid gas-permeable lens (piggyback system) for photophobia and low vision correction after traumatic aniridia and aphakia. A 40-year-old woman was referred to our practice for contact lens fitting in her right eye, which was left aphakic after an open globe injury. She also presented traumatic aniridia in the right eye, and her left eye had been previously eviscerated. A successful fitting was obtained with a photochromic silicone hydrogel (senofilcon A) contact lens, with a Dk/t of 121 × 10-9, under an aspheric design, +13.00 D rigid gas-permeable lens. The patient displayed visual acuity and contrast sensitivity improvement and reported decreased photophobia.

Cortical Visual Mapping following Ocular Gene Augmentation Therapy for Achromatopsia.

The ability of the adult human brain to develop function following correction of congenital deafferentation is controversial. Specifically, cases of recovery from congenital visual deficits are rare. CNGA3-achromatopsia is a congenital hereditary disease caused by cone-photoreceptor dysfunction, leading to impaired acuity, photoaversion, and complete color blindness. Essentially, these patients have rod-driven vision only, seeing the world in blurry shades of gray. We use the uniqueness of this rare disease, in which the cone-photoreceptors and afferent fibers are preserved but do not function, as a model to study cortical visual plasticity. We had the opportunity to study two CNGA3-achromatopsia adults (one female) before and after ocular gene augmentation therapy. Alongside behavioral visual tests, we used novel fMRI-based measurements to assess participants' early visual population receptive-field sizes and color regions. Behaviorally, minor improvements were observed, including reduction in photoaversion, marginal improvement in acuity, and a new ability to detect red color. No improvement was observed in color arrangement tests. Cortically, pretreatment, patients' population-receptive field sizes of early visual areas were untypically large, but were decreased following treatment specifically in the treated eye. We suggest that this demonstrates cortical ability to encode new input, even at adulthood. On the other hand, no activation of color-specific cortical regions was demonstrated in these patients either before or up to 1 year post-treatment. The source of this deficiency might be attributed either to insufficient recovery of cone function at the retinal level or to challenges that the adult cortex faces when computing new cone-derived input to achieve color perception.SIGNIFICANCE STATEMENT The possibility that the adult human brain may regain or develop function following correction of congenital deafferentation has fired the imagination of scientists over the years. In the visual domain, cases of recovery from congenital deficits are rare. Gene therapy visual restoration for congenital CNGA3-achromatopsia, a disease caused by cone photoreceptor dysfunction, gave us the opportunity to examine cortical function, to the best of our knowledge for the first time, both before and after restorative treatment. While behaviorally only minor improvements were observed post-treatment, fMRI analysis, including size algorithms of population-receptive fields, revealed cortical changes, specifically receptive field size decrease in the treated eyes. This suggests that, at least to some degree, the adult cortex is able to encode new input.

Automated Keratopigmentation in Boston Type 1 Keratoprosthesis: An Aesthetic Alternative.

Two male patients, aged 64 and 55 years old, presented at the cornea department for a Boston type 1 keratoprosthesis (Kpro I) implantation after multiple corneal graft failures. After surgery, they achieved a best corrected visual acuity of 20/200 and 20/150, respectively. However, they manifested photophobia and aesthetic complaints. Both patients underwent keratopigmentation to improve the aesthetic outcome using vegetable pigments, after mechanical corneal deepithelization, with no intraoperative or postoperative incidents or adverse events. After 1-year follow-up, the patients presented the same best corrected visual acuity with improvement of the aesthetic outcome.

Sensory Sensitivity in TBI: Implications for Chronic Disability.

PURPOSE OF REVIEW: This review investigates the relationship between sensory sensitivity and traumatic brain injury (TBI), and the role sensory sensitivity plays in chronic disability. RECENT FINDINGS: TBI is a significant cause of disability with a range of physical, cognitive, and mental health consequences. Sensory sensitivities (e.g., noise and light) are among the most frequently reported, yet least outwardly recognizable symptoms following TBI. Clinicians and scientists alike have yet to identify consistent nomenclature for defining noise and light sensitivity, making it difficult to accurately and reliably assess their influence. Noise and light sensitivity can profoundly affect critical aspects of independent function including communication, productivity, socialization, cognition, sleep, and mental health. Research examining the prevalence of sensory sensitivity and evidence for the association of sensory sensitivity with TBI is inconclusive. Evidence-based interventions for sensory sensitivity, particularly following TBI, are lacking.

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.

Treatment of ocular rosacea.

Although rosacea is a common entity with significant cosmetic, socioeconomic, and vision-threatening impacts, this disorder remains incurable. Furthermore, until quite recently many of the therapeutic options for rosacea had not been assessed through rigorous clinical testing with meaningful outcome measures. Nonetheless, new medical and surgical interventions that have been validated in well-designed trials hold the promise of treating rosacea more effectively. Furthermore, recent enhancements in our understanding of the cellular and molecular biology offer highly translational insights that will hopefully lead to the development of new treatment options for rosacea. We review the evidence for these therapies and discuss new scientific findings that can be exploited for new therapeutic interventions.

Noninvasive Electrical Stimulation for the Treatment of Chronic Ocular Pain and Photophobia.

INTRODUCTION: "Dry eye" or "keratoconjunctivitis sicca" is a multifactorial disease estimated to have a worldwide prevalence of 5-33%. Conventional therapies targeting the ocular surface with artificial tears, anti-inflammatories, punctal closure, eyelid hygiene, and antibiotics do not provide relief in all patients, especially those with neuropathic-like ocular complaints (wind hyperalgesia and photophobia). We anticipated that ocular transcutaneous electrical nerve stimulation (TENS) would alleviate symptoms of ocular pain, photophobia, and dryness in these latter individuals. METHODS: All individuals who received electrical stimulation between May 10, 2016 and April 6, 2017 for the treatment of chronic ocular pain at the oculofacial pain clinic of the Miami Veterans Administration Hospital were included in this retrospective review. All patients had symptoms of dryness along with other neuropathic-like symptoms (e.g., photophobia) and minimal signs of tear dysfunction. Ocular pain intensity, symptoms of dryness, and light sensitivity were compared pre-treatment and five min post-treatment via a two-tailed paired Student's t-test. RESULTS: The use of TENS significantly reduced the mean pain intensity in both the right and left eyes five min after treatment compared to prior to treatment (p < 0.05, paired t-test). The use of TENS significantly decreased light sensitivity in both eyes (p < 0.05). The findings for symptoms of dryness, however, were equivocal with a significant decrease in the left eye but not the right (p < 0.05, paired t-test). DISCUSSION: Our data indicate that TENS may similarly provide analgesia in patients with dry eye symptoms as it does for many other chronic pain conditions. Furthermore, the noted effect on symptoms of photophobia and dryness suggest that all may be linked by similar trigeminal-thalamic-cortical pathways. Prospective studies with electrical stimulation of dry eye are needed to further elucidate its benefit and mechanism of action.

Transcranial static magnetic field stimulation (tSMS) of the visual cortex decreases experimental photophobia.

Background Transcranial static magnetic field stimulation (tSMS) reduces cortical excitability in humans. Methods The objective of this study was to determine whether tSMS over the occipital cortex is effective in reducing experimental photophobia. In a sham-controlled double-blind crossover study, tSMS (or sham) was applied for 10 minutes with a cylindrical magnet on the occiput of 20 healthy subjects. We assessed subjective discomfort induced by low-intensity and high-intensity visual stimuli presented in a dark room before, during and after tSMS (or sham). Results Compared to sham, tSMS significantly reduced the discomfort induced by high-intensity light stimuli. Conclusions The visual cortex may contribute to visual discomfort in experimental photophobia, providing a rationale for investigating tSMS as a possible treatment for photophobia in migraine.

Updated strategies for the management, pathogenesis and molecular genetics of different forms of ichthyosis syndromes with prominent hair abnormalities.

Syndromic ichthyosis is rare inherited disorders of cornification with varied disease complications. This disorder appears in seventeen subtypes associated with severe systematic manifestations along with medical, cosmetic and social problems. Syndromic ichthyosis with prominent hair abnormalities covers five major subtypes: Netherton syndrome, trichothiodystrophy, ichthyosis hypotrichosis syndrome, ichthyosis hypotrichosis sclerosing cholangitis and ichthyosis follicularis atrichia photophobia syndrome. These syndromes mostly prevail in high consanguinity states, with distinctive clinical features. The known pathogenic molecules involved in ichthyosis syndromes with prominent hair abnormalities include SPINK5, ERCC2, ERCC3, GTF2H5, MPLKIP, ST14, CLDN1 and MBTPS2. Despite underlying genetic origin, most of the health professionals solely rely on phenotypic expression of these disorders that leads to improper management of patients, hence making these patients living an orphanage life. After dermal features, association of other systems such as nervous system, skeletal system, hair abnormalities or liver problems may sometimes give clues for diagnosis but still leaving place for molecular screening for efficient diagnosis. In this paper, we have presented a review of ichthyosis syndrome with prominent hair abnormalities, with special emphasis on their updated genetic consequences and disease management. Additionally, we aim to update health professionals about the practice of molecular screening in ichthyosis syndromes for appropriate diagnosis and treatment.

Diagnosis, pathophysiology, and treatment of photophobia.

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.

Blepharospasm in children and adolescents.

PURPOSE: Benign essential blepharospasm (BEB) generally is considered a disorder of adults; however, it rarely can present in childhood or adolescence. The main purpose of this study was to determine the prevalence of BEB in children and adolescents. Our research question was whether blepharospasm is seen in children or adolescents as well as in the adult population. METHODS: We conducted a retrospective chart review at the University of Utah and Johns Hopkins University. We reviewed our databases for diagnoses of blepharospasm and tic disorder over the past 10 years in patients of all ages. Charts then were reviewed to confirm the diagnosis, and a questionnaire was sent to subjects whose blepharospasm had apparently begun before age 20 years. RESULTS: We identified 26 patients diagnosed with eyelid spasms that had begun while under the age of 20. We confirmed BEB in four of these cases. Of these individuals, all had developed symptoms in adolescence or before and all were still symptomatic but had noted improvement in the severity and frequency of their symptoms. CONCLUSIONS: Although rare, BEB can develop in the first decade of life, producing symptoms and signs that are similar to adults, with persistence into adulthood.

Red-Tinted Contact Lenses May Improve Quality of Life in Retinal Diseases.

Supplemental digital content is available in the text. ABSTRACT: To determine the benefits provided by centrally red-tinted contact lenses on visual acuity, contrast sensitivity (CS), photophobia, and quality of life in patients with degenerative retinal diseases.We evaluated the impact of centrally red-tinted hydrogel contact lenses on nine patients (aged 15 to 22 years) with severe photophobia and poor visual acuity. Each patient underwent a full eye examination with and without contact lenses, including visual acuity at distance and near, CS, eye movement recording for nystagmus, refraction, and a fundus examination. All patients completed a low vision-adapted VFQ 25-Version 2000 quality-of-life questionnaire.Seven of nine patients demonstrated improvement in binocular visual acuity as well as improvement in CS with the tinted contact lenses. Subjectively, all patients described a major improvement in their photophobia both outdoors and indoors, as well as a marked improvement in quality of life.Red-tinted contact lenses may dramatically improve visual functions, outdoor performance, and quality of life of patients suffering from retinal diseases. These lenses should be a part of the regular assessment in specialty clinics treating patients with low vision, glare, and photophobia.

[An Unusual Cause of Increased Light Sensitivity]. / Eine ungewöhnliche Ursache für erhöhte Blendempfindlichkeit.

Photophobia is in many cases linked to pathologies of the anterior segment of the eye, e.g. cataract or iritis. We report an unusual case of increased light sensitivity due to a compressing lesion of the chiasm. Pituitary adenomas are among the most frequent intracranial tumours and can affect the chiasm - the site where all the visual afferences meet. A lesion of the chiasm is therefore particularly dangerous. Fortunately, in two-thirds of all cases, pituitary adenomas lead to hormonal dysfunction, so that magnetic resonance imaging of the brain is conducted. However, in the remainder of the cases, the ophthalmologist may be the first physician to see the patient because of visual problems. Usually patients report reduced vision or show typical visual field defects, such as bitemporal hemianopsia. However, the only pathological symptom may be increased light sensitivity. In rare cases of photophobia which cannot be explained by pathologies of the anterior segment, a compressing lesion of the chiasm should be considered.

Single-pulse transcranial magnetic stimulation (sTMS) for the acute treatment of migraine: evaluation of outcome data for the UK post market pilot program.

BACKGROUND: Single pulse transcranial magnetic stimulation (sTMS) is a novel treatment for acute migraine. Previous randomised controlled data demonstrated that sTMS is effective and well tolerated in the treatment of migraine with aura. The aim of the programme reported here was to evaluate patient responses in the setting of routine clinical practice. METHODS: Migraine patients with and without aura treating with sTMS had an initial review (n = 426) and training call, and then participated in telephone surveys at week six (n = 331) and week 12 during a 3-month treatment period (n = 190). RESULTS: Of patients surveyed with 3 month data (n = 190; episodic, n = 59; chronic, n = 131), 62 % reported pain relief, finding the device effective at reducing or alleviating migraine pain; in addition there was relief reported of associated features: nausea- 52 %; photophobia- 55 %; and phonophobia- 53 %. At 3 months there was a reduction in monthly headache days for episodic migraine, from 12 (median, 8-13 IQ range) to 9 (4-12) and for chronic migraine, a reduction from 24 (median, 16-30 IQ range) to 16 (10-30). There were no serious or unanticipated adverse events. CONCLUSION: sTMS may be a valuable addition to options for the treatment of both episodic and chronic migraine.

Femtosecond laser-assisted keratopigmentation for the management of visual disabilities due to peripheral iridectomies.

PURPOSE: To report the technique and result of keratopigmentation using a femtosecond laser for the treatment of functional visual disabilities caused by peripheral iridectomies. DESIGN: Case report. METHODS: Two eyes of 2 patients underwent femtosecond laser-assisted keratopigmentation (FLAK) for moderate to severe visual dysfunction secondary to peripheral iridectomies. The main outcomes measures of the study were changes in visual-related symptoms, cosmesis, and intraoperative surgical complications. RESULTS: Following FLAK, the visual-related symptoms (ghosting, glare, and monocular diplopia) improved in both cases with significant improvement to total elimination of symptoms. No patient lost any lines of visual acuity, and no significant complications were observed during the follow-up period. The cosmetic appearance was reported as very good. CONCLUSIONS: FLAK is minimally invasive and results in a significant decrease in the subjective glare and photophobia and even in resolution of monocular diplopia. The cosmetic outcome was also favorable. This technique allows surgeons to correct visual disabilities associated with iris defects with a high success rate while avoiding more aggressive intraocular surgery.