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.

Original Contribution Section Editors: Clare Fraser, MD Susan Mollan, MD The Unmet Challenge of Diagnosing and Treating Photophobia Thomas M. Buchanan, MD, Kathleen B. Digre, MD, Judith E. A. Warner, MD, Bradley J. Katz, MD, PhD 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. Journal of Neuro-Ophthalmology 2022;42:372–377 doi: 10.1097/WNO.0000000000001556 © 2022 by North American Neuro-Ophthalmology Society Department of Neurology (TB, KBD, JEAW, BJK), University of Utah Health Sciences Center, Salt Lake City, Utah; and Department of Ophthalmology and Visual Sciences (KBD, JEAW, BJK), John A Moran Eye Center, University of Utah Health Sciences Center, Salt Lake City, Utah. Dr. Buchanan is now with the Neurology of Eastern Utah, Ashley Medical Group, Vernal, Utah. Supported in part by an unrestricted grant from Research to Prevent Blindness, New York, NY, to the Department of Ophthalmology and Visual Sciences, University of Utah. This investigation was also supported by a generous gift from the Mostaghel family. K. B. Digre, J. E. A. Warner, and B. J. Katz received royalties from a patent describing optical filters for the treatment of photophobia; B. J. Katz is named on a patent describing the use of nanoparticle filters for the treatment of photophobia; B. J. Katz is the CEO of Axon Optics, LLC, an online company that develops and markets eyewear for photophobia. The remaining author reports no conflicts of interest. Address correspondence to Bradley J. Katz, MD, PhD, John A. Moran Eye Center, 65 Mario Capecchi Drive, Salt Lake City, UT 84132; E-mail: [e-mail] 372 P hotophobia, an abnormal sensitivity to light, is associated with a number of ocular conditions, and most ophthalmologists or optometrists (“eye care providers”) have no problem diagnosing and treating these conditions. Ocular conditions associated with photophobia, such as benign essential blepharospasm, dry eye, uveitis, and ocular albinism, all have examination findings that point the eye care provider toward the correct diagnosis. However, photophobia is also associated with a number of neurologic diagnoses (1) that may be associated with a normal eye examination, such as migraine, traumatic brain injury (TBI) (2), and pituitary tumors (3). Here, eye care providers may be less wellequipped to determine the cause of the patient’s symptoms. By the same token, neurologists will be more facile at diagnosing the neurologic causes of photophobia and less adept at identifying the ocular causes of photophobia. For these reasons, and because of the other numerous causes of photophobia (Table 1), neuro-ophthalmologists are sometimes called on to help diagnose and treat patients with photophobia. We hypothesized that if we could better understand the most common causes of photophobia in our patient population, we could better equip eye care providers and neurologists to diagnose and treat the conditions they are most likely to encounter. METHODS This retrospective chart review was approved by the University of Utah’s Institutional Review Board. Using billing records, we identified all patients given a diagnosis of visual discomfort (ICD-9 368.13) during a visit at the Department of Ophthalmology and Visual Sciences’ John A Moran Eye Center, part of University of Utah Health in Salt Lake City, Utah, during the years 2001–2009 (there is not a specific ICD-9 code for “photophobia”). We reviewed these charts to determine which of them specifically mentioned photophobia or light sensitivity as one of their primary symptoms in the history, or if photophobia was noted during the examination, or as part of the assessment. These patient charts were reviewed using a standardized Buchanan et al: J Neuro-Ophthalmol 2022; 42: 372-377 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Original Contribution TABLE 1. Conditions associated with photophobia (adapted in part from Digre and Brennan, 2012 (4)) Ocular conditions Anterior segment Iritis/uveitis Conjunctivitis Corneal neuropathy Corneal dystrophy Blepharitis Bilateral acute transillumination defects of the iris Dry eye syndrome Pterygia Interstitial keratitis (Cogan syndrome) Keratitis Posterior segment Vitritis Photoreceptor dysfunction/retinal dystrophy (including albinism, achromatopsia, cone dystrophy, retinitis pigmentosa) Alström syndrome Sjogren–Larsson syndrome Sympathetic ophthalmia Optic nerve Optic neuritis Papilledema (pseudotumor cerebri syndrome) Chiasm Pituitary tumor Pituitary apoplexy Hypophysitis Occipital lobe Hyperexcitability Neurologic conditions Migraine Benign essential blepharospasm Progressive supranuclear palsy Traumatic brain injury Meningeal irritation (meningitis, subarachnoid hemorrhage) Intracranial hypertension or hypotension form, and the deidentified data were entered into an Excel spreadsheet (Microsoft, Inc, Redmond, WA). Using the first clinic visit that mentioned light sensitivity, we collected demographic data (sex, age, employment, and disability status), presenting symptoms, medical history (headaches, migraines, TBI, ocular surgery, neurologic surgery, neurologic illness, or antidepressant medication use), examination findings, assessment, and plan. If the light sensitivity was associated with an injury, this information was also collected. Children were defined as age 0–17 years, and adults included all patients 18 years and older. RESULTS A total of 198 charts were identified for review. Thirtyfive charts had been miscoded and did not mention photophobia or light sensitivity. Sixteen charts could not Buchanan et al: J Neuro-Ophthalmol 2022; 42: 372-377 Carotid artery dissection Stroke Reversible cerebral vasoconstriction syndrome (RCVS) Thalamic diseases (tumor, stroke, hemorrhage) HaNDL syndrome (transient headache and neurological deficits with cerebrospinal fluid lymphocytosis) Psychiatric conditions Agoraphobia Anxiety disorder Panic disorder Depression Hang-over headache Medications Barbiturates Benzodiazepines Chloroquine Methylphenidate Haldol Lithium Linezolid Zoledronate Sildenafil Narcotics (heroin, opioids) Miscellaneous conditions Neurasthenia (chronic fatigue) Fibromyalgia Measles Rabies Lyme disease Inflammatory bowel disease IFAP syndrome (ichthyosis follicularis with alopecia and photophobia) PPK (psoriasiform lesions and palmoplantar keratoderma) Serotonin syndrome Complex regional pain syndrome Trisomy 18 Zinc deficiency with exocrine insufficiency be located or had incomplete records, leaving 147 records for inclusion. Our population included 58 adult women, 53 adult men, 22 girls, and 14 boys. The mean age at presentation to the clinic was 37 years (range 6 months– 94 years). Of 111 adults, the mean age at presentation was 46.8 years, and the average age of onset of photophobia was 37.4 years. Of 36 children, the mean age at presentation was 7.4 years, and the mean age of onset of photophobia was 6.3 years. Photophobia was the chief complaint for 133 (90.5%) of the 147 patients. Ten men and 3 women attributed their photophobia to a recent injury. Seven men and 1 woman attributed their photophobia to an injury sustained in the workplace. Other common presenting complaints recorded in the history of the present illness included headache (n = 94; 63.9%), blurry vision (n = 34; 23.1%), dry eyes (n = 18; 12.2%), eye pain (n = 15; 10.2%), and diplopia (n = 8; 5.4%). 373 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Original Contribution The medical history revealed 13 patients with a history of TBI (8.8%), 19 patients with a family history of migraine (12.9%), and 42 patients using antidepressant medications (28.6%). Of the 111 adults, 67 records had information regarding employment history: 41 of these 67 patients (61.2%) indicated they were employed. One man and 1 woman reported that they were disabled specifically because of their photophobia. Twenty-seven adults (24.3%) and 19 children (52.8%) had a normal ocular examination. Common abnormalities noted in the ocular examination included blepharitis (n = 6; 4.1%), punctate corneal epithelial erosions (N = 5; 3.4%), and blepharospasm (N = 4; 2.7%). In the records reviewed, the eye care provider evaluating the patient may have listed more than 1 diagnosis as a cause for the patient’s photophobia. The most common diagnoses included migraine headache (N = 79; 53.7%), followed by dry eye syndrome (N = 53; 36.1%), ocular trauma (N = 12; 8.2%), progressive supranuclear palsy (N = 10; 6.8%), and TBI (N = 6; 4.1%). Depression was noted as possibly contributing to photophobia in 13 patients (8.8%). Other miscellaneous diagnoses included central dazzling (N = 2); Meige syndrome (N = 1); the syndrome of headache, neurological deficit, and cerebrospinal fluid lymphocytosis (HaNDL; N = 1); and Kabuki syndrome (N = 1). In 38 records (25.9%), the examining physician did not list any cause for the photophobia. These 38 records included 13 adults (11.7% of adults) and 25 children (69.4% of children). Treatment was generally directed at the underlying condition, including preventative migraine medications for patients with photophobia ascribed to migraine, artificial tears for patients with dry eye syndrome, and botulinum toxin injections for patients with blepharospasm. CONCLUSIONS In our review of 147 patients presenting for evaluation of photophobia, just over one-half of patients were diagnosed with migraine and more than one-third of patients were diagnosed with dry eye. What is more striking is the significant number of patients, especially children, who left the clinic without any diagnosis or treatment for their photophobia. This observation indicates that eye care providers, especially those caring for children, may not know the most common causes of photophobia and therefore may not know what history questions to ask and what examination techniques to use to identify these most common causes. Identifying the most common causes of photophobia in a retrospective review such as this one is the first step at addressing this knowledge gap, and as a result of this study, our group is currently working to address this knowledge gap by developing a curriculum to teach eye care providers how to approach patients with photophobia in the presence of a normal eye examination. We have previously published a 374 flow diagram that may assist physicians caring for patients with a primary complaint of photophobia (Fig. 1). The second step in addressing this knowledge gap is to better understand the pathophysiology of photophobia. Because these data were collected, our group and others have published reviews on the pathophysiology of photophobia (4,5), as well as our current understanding of the diagnosis, pathophysiology, and treatment of photophobia (2,6). Taken together, these reviews and this retrospective study support the significant role that migraine plays in the pathophysiology of photophobia. Patients with migraine often identify photophobia as the most bothersome symptom, following headache (7), and patients with migraine have a lower threshold to light sensitivity compared with a control cohort (8). Because migraine is a neurologic disease, ophthalmologists and optometrists may be less familiar with its diagnosis and treatment. The 3-item ID-migraine questionnaire is a quick way for nonneurologists to screen a patient for migraine (9). The 3 questions are, “Has a headache limited your activities for a day or more in the last 3 months?”, “Are you nauseated or sick to your stomach when you have a headache?”, and “Does light bother you when you have a headache?” Answering “yes” to all 3 of these questions identifies migraine headache with a sensitivity of 81%, a specificity of 75%, and a positive predictive value of 93%. In our experience, asking about a personal history of being carsick in childhood, unexplained abdominal pain in childhood, or a family history of migraine or headache may also help point the clinician toward a diagnosis of migraine, especially in the presence of a normal ocular examination. If unfamiliar with the diagnosis and treatment of migraine, the examining physician may refer the patient back to their primary care physician or to a neurologist. FL-41 tinted lenses have been shown to be an effective treatment in children with migraine (10). Precision optical tints also show promise in the reduction of cortical hyperactivation in migraine (11). Traumatic brain injury is another cause of photophobia that may be underrecognized. Survivors of mild TBI report noise and light sensitivity that adversely affects healthrelated quality of life (12), and blast-injured veterans with mild TBI have increased sensory sensitivity, including photophobia (13). Patients with photophobia associated with mild TBI often have coexisting posttraumatic headache or posttraumatic migraine (14). These patients can benefit from referral to a comprehensive brain injury clinic where a variety of treatment modalities may be used to address the multiple psychological, cognitive, and somatic problems associated with mild TBI. Dry eye syndrome was another frequent diagnosis that may be easily identified and treated by neurologists as well as eye care providers. In a cohort of 19 patients with chronic migraine, we found that all of them had symptoms of dry eye, but that none of them had objective signs of dry eye syndrome (15). The 5-item Dry Eye Questionnaire (DEQ5) has been shown to be an effective screening instrument Buchanan et al: J Neuro-Ophthalmol 2022; 42: 372-377 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Original Contribution FIG. 1. An approach to the patient with photophobia. Adapted from Digre and Brennan, 2012 (4). This algorithm may aid clinicians in diagnosing and treating patients with photophobia, especially in the presence of a normal eye examination. HA = headache; SLE = slitlamp examination. for dry eye syndrome (16). However, because dry eye is often easily treated with over-the-counter artificial tears, recommendation of this treatment to a patient with photophobia may be both diagnostic and therapeutic. Diel et al have recently postulated that the photophobia associated with migraine, dry eye, and traumatic brain injury may share a common neuroanatomic pathway (17). Benign essential blepharospasm is usually recognized during the clinical examination but may be missed if the patient is asymptomatic during the encounter. Because nearly all patients (94%) with blepharospasm report photophobia (18,19), asking patients with photophobia about frequent blinking, squeezing of the eyelids, and difficulty keeping the eyelids open may be helpful. Like patients with migraine, Buchanan et al: J Neuro-Ophthalmol 2022; 42: 372-377 we have previously demonstrated that patients with blepharospasm have a reduced threshold to light sensitivity compared with controls (20) and that FL-41 tinted lenses can reduce blink frequency, light sensitivity, and functional limitations in patients with blepharospasm (21). Clinicians evaluating patients with photophobia should be on the lookout for mental health conditions that may accompany some of these underlying diseases. Previously, we have demonstrated an increased incidence of depression and anxiety in patients with photophobia (22). Patients with TBI may have posttraumatic stress disorder associated with their injury in addition to depression and anxiety (13). Mental health comorbidities are prevalent in patients with migraine and light sensitivity (23). Medications are 375 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Original Contribution sometimes associated with photophobia (Table 1), but in our cohort, medications were not documented as the cause of any patient’s photophobia. Although none of the patients in our cohort were ultimately diagnosed with an optic nerve disease, optic nerve diseases can be associated with photophobia (Table 1), and clinicians evaluating a patient with photophobia should be on the lookout for optic neuritis and other diseases of the optic nerve. Children, especially if they cannot be adequately examined during the encounter, present a special challenge. Migraine is underdiagnosed and misdiagnosed in children (24,25), so asking these patients or their families about headaches, carsickness, unexplained abdominal pain, and a family history of migraine or headache, may point the clinician toward this diagnosis. Although less common in children compared with adults, dry eye syndrome may be diagnosed and treated with over-the-counter artificial tears. Similarly, while it is primarily considered a disease of adults, we have described benign essential blepharospasm in children (26). Because of the uncommon but potentially sight-threatening causes of photophobia in children, such as congenital glaucoma (27) cone dystrophy, and uveitis (28), an examination under anesthesia may be required when the ocular examination is limited by the patient’s ability to cooperate. Limitations This study is limited by its retrospective nature and our inability to determine the cause of photophobia in the significant number of patients who remained undiagnosed at the end of their encounter(s). A study in which these patients could be called back for a more definitive diagnosis would more accurately represent the most common causes of photophobia. Because this study was conducted at a tertiary eye center, the results may not be generalizable to other patient populations. Future Studies We are currently studying vision-related quality of life in patients with photophobia (29). We are also developing a curriculum for diagnosing and treating photophobia in adults and children. We hope that a better understanding of the most common causes of photophobia, the pathophysiology of photophobia, and the impact of photophobia on vision-related quality of life will help us better address the knowledge gap identified in this study. STATEMENT OF AUTHORSHIP Category 1: a. Conception and design: T. Buchanan, K. B. Digre, J. E. A. Warner, and B. J. Katz; b. Acquisition of data: T. Buchanan; c. Analysis and interpretation of data: T. Buchanan, K. B. Digre, J. E. A. Warner, and B. J. Katz. Category 2: a. Drafting the manuscript: T. Buchanan, K. B. Digre, and B. J. Katz; b. Revising it for intellectual content: K. B. Digre and B. J. Katz. Category 3: a. Final approval of the completed manuscript: T. Buchanan, K. B. Digre, J. E. A. Warner, and B. J. 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