Photophobia Contributes to Migraine-Associated Disability and Reduced Work Productivity: Results From the American Registry for Migraine Research (ARMR)

Background: Photosensitivity, often called "photophobia" in the migraine literature, is a common and bothersome symptom for most people during their migraine attacks. This study aimed to investigate the association of photophobia severity with work productivity, activity impairment, and migraine-associated disability using data from a large cohort of patients with migraine who were enrolled into the American Registry for Migraine Research (ARMR). Methods: This study used Photosensitivity Assessment Questionnaire (PAQ) scores to investigate the relationship between photophobia severity with work productivity and activity impairment (using the Work Productivity and Activity Impairment [WPAI] questionnaire) and migraine-related disability (using the Migraine Disability Assessment [MIDAS]) among those with migraine. Summary statistics are presented as means and standard deviations for variables that were normally distributed and as medians and interquartile ranges for variables that were not normally distributed. Multiple linear regression models were developed to measure the relationships between photophobia scores with work productivity and activity impairment and migraine-associated disability, controlling for age, sex, headache frequency, headache intensity, anxiety (using the generalized anxiety disorder [GAD-7]), and depression (using the Patient Health Questionnaire [PHQ-2]). Results: One thousand eighty-four participants were included. Average age was 46.1 (SD 13.8) years, 87.2% (n = 945) were female, average headache frequency during the previous 90 days was 44.3 (SD 29.9), average headache intensity was 5.9 (SD 1.7), median PHQ-2 score was 1 (IQR 0-2), and median GAD-7 was 5 (IQR 2-8). Mean PAQ score was 0.47 (SD 0.32), and median MIDAS score was 38 (IQR 15.0-80.0). Among the 584 employed participants, 47.4% (n = 277) reported missing work in the past week because of migraine, mean overall work impairment was 42.8% (SD 26.7), mean activity impairment was 42.5% (SD 26.2), mean presenteeism score was 38.4% (SD 24.4), and median absenteeism was 0 (IQR 0-14.5). After controlling for age, sex, headache frequency, average headache intensity, PHQ-2 score, and GAD-7 score, there was a statistically significant association between photophobia scores with: a) MIDAS scores (F[7,1028] = 127.42, P < 0.001, R 2 = 0.461, n = 1,036); b) overall work impairment (F[7,570] = 29.23, P < 0.001, R 2 = 0.255, n = 578); c) activity impairment (F[7,570] = 27.42, P < 0.001, R 2 = 0.243, n = 578); d) presenteeism (F[7,570] = 29.17, P < 0.001, R 2 = 0.255, n = 578); and e) absenteeism for the zero-inflated ( P = 0.003) and negative binomial ( P = 0.045) model components ( P < 0.001, n = 578). Conclusions: In those with migraine, severe photophobia is associated with reduced work productivity and higher presenteeism, absenteeism, activity impairment, and migraine-related disability.

Original Contribution Section Editors: Clare Fraser, MD Susan Mollan, MD Photophobia Contributes to Migraine-Associated Disability and Reduced Work Productivity: Results From the American Registry for Migraine Research (ARMR) Zachary Leibovit-Reiben, BS, Gina Dumkrieger, PhD, David W. Dodick, MD, Kathleen Digre, MD, Catherine D. Chong, PhD, Meesha Trivedi, BS, Todd J. Schwedt, MD Background: Photosensitivity, often called “photophobia” in the migraine literature, is a common and bothersome symptom for most people during their migraine attacks. This study aimed to investigate the association of photophobia severity with work productivity, activity impairment, and migraine-associated disability using data from a large cohort of patients with migraine who were enrolled into the American Registry for Migraine Research (ARMR). Methods: This study used Photosensitivity Assessment Questionnaire (PAQ) scores to investigate the relationship between photophobia severity with work productivity and activity impairment (using the Work Productivity and Activity Impairment [WPAI] questionnaire) and migraine-related disability (using the Migraine Disability Assessment [MIDAS]) among those with migraine. Summary statistics are presented as means and standard deviations for variables that were normally distributed and as medians and interquartile ranges for variables that were not normally distributed. Multiple linear regression models were developed to measure the relationships between photophobia scores with work productivity and activity impairment and migraine-associated disability, controlling for age, sex, headache frequency, headache intensity, anxiety (using the generalized anxiety disorder [GAD-7]), and depression (using the Patient Health Questionnaire [PHQ-2]). Results: One thousand eighty-four participants were included. Average age was 46.1 (SD 13.8) years, 87.2% (n = 945) were female, average headache frequency during the previous 90 days was 44.3 (SD 29.9), average headache intensity was 5.9 (SD 1.7), median PHQ-2 score was 1 (IQR 0–2), and median GAD-7 was 5 (IQR 2–8). Mean PAQ score was 0.47 (SD 0.32), and median MIDAS score was 38 (IQR 15.0–80.0). Among the 584 employed participants, 47.4% (n = 277) reported missing work in the past week because of migraine, mean overall work impairment was 42.8% (SD 26.7), mean activity impairment was 42.5% (SD 26.2), mean presenteeism score was 38.4% (SD 24.4), and median absenteeism was 0 (IQR 0–14.5). After controlling for age, sex, headache frequency, average headache intensity, PHQ-2 score, and GAD-7 score, there was a statistically significant association between photophobia scores with: a) Mayo Clinic (ZL-R, GD, DWD, CDC, MT, TJS), Phoenix, Arizona; University of Arizona College of Medicine—Tucson (ZL-R), Tucson, Arizona; and Department of Neurology (KD), University of Utah, Salt Lake City, Utah. The American Migraine Foundation provided data from the American Registry for Migraine Research (ARMR) to conduct this research. The analyses and interpretation of ARMR data are the responsibility of the authors and in no way should be seen as an official interpretation, endorsement by or position of ARMR or the American Migraine Foundation. Z. Leibovit-Reiben reports no conflicts of interest. G. Dumkrieger has received research funding from Amgen. D. W. Dodick reports the following conflicts within the past 12 months: Consulting: Amgen, Allergan, Abbvie, Lundbeck, Biohaven, Pfizer, Atria Health, CapiThera Ltd., Cerecin, Cooltech, Ceruvia Lifesciences LLC, Ctrl M, Allergan, Biohaven, GSK, Lundbeck, Eli Lilly, Novartis, Impel, Satsuma, Theranica, WL Gore, Nocira, Perfood, Praxis, AYYA Biosciences, Revance. Payment or honoraria for lectures, presentations, educational events: Amgen, Novartis, Eli Lilly, Teva, Allergan, Abbvie, Lundbeck, Biohaven, Pfizer. Participation on a Data Safety Monitoring Board or Advisory Board: Amgen, Novartis, Eli Lilly, Allergan, Abbvie, Lundbeck, Biohaven Honoraria: Vector psychometric Group, Clinical Care Solutions, CME Outfitters, Curry Rockefeller Group, DeepBench, Global Access Meetings, KLJ Associates, Academy for Continued Healthcare Learning, Majallin LLC, Medlogix Communications, MJH Lifesciences, Miller Medical Communications, WebMD Health/Medscape, Wolters Kluwer, Oxford University Press, Cambridge University Press. Research Support: Department of Defense, National Institutes of Health, Henry Jackson Foundation, Sperling Foundation, American Migraine Foundation, Patient Centered Outcomes Research Institute (PCORI). Leadership or fiduciary role in other board, society, committee or advocacy group, paid or unpaid: American Migraine Foundation. American Brain Foundation. International Headache Society Global Patient Advocacy Coalition Stock Options/Shareholder/Patents/Board of Directors: Aural analytics (options), ExSano (options), Man and Science (options), Healint (Options), Theranica (Options), Second Opinion/Mobile Health (Options), Epien (Options/Board), Nocira (options), Matterhorn (Shares/Board), Ontologics (Shares/Board), King-Devick Technologies (Options/Board), Precon Health (Options/Board), AYYA Biosciences (Options), Atria Health (options). Patent 17189376.1–1,466:vTitle: Botulinum Toxin Dosage Regimen for Chronic Migraine Prophylaxis (Non-royalty bearing). Patent application submitted: Synaquell (Precon Health). T. Schwedt, within the last 12 months, has served as a consultant for Abbvie, Allergan, Amgen, Axsome, Biodelivery Science, Biohaven, Collegium, Eli Lilly, Linpharma, Lundbeck, Satsuma, and Theranica. He has stock options in Aural Analytics and Nocira. He has received royalties from UpToDate. He has received research funding from: American Migraine Foundation, Amgen, Henry Jackson Foundation, Mayo Clinic, National Institutes of Health, Patient Centered Outcomes Research Institute, SPARK Neuro, and U.S. Department of Defense. He serves on the Board of Directors for the American Headache Society and the American Migraine Foundation. K. Digre is supported in part by an Unrestricted Grant from Research to Prevent Blindness, New York, NY, to the Department of Ophthalmology & Visual Sciences, University of Utah. C. D. Chong reports research funding from Amgen, the Department of Defense and The National Institutes of Health. Address correspondence to Todd J. Schwedt, MD, Mayo Clinic, 5777 E Mayo Boulevard, Phoenix, AZ 85054; E-mail: [e-mail] Leibovit-Reiben et al: J Neuro-Ophthalmol 2024; 44: 259-266 259 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Original Contribution MIDAS scores (F[7,1028] = 127.42, P , 0.001, R2 = 0.461, n = 1,036); b) overall work impairment (F[7,570] = 29.23, P , 0.001, R2 = 0.255, n = 578); c) activity impairment (F[7,570] = 27.42, P , 0.001, R2 = 0.243, n = 578); d) presenteeism (F[7,570] = 29.17, P , 0.001, R2 = 0.255, n = 578); and e) absenteeism for the zeroinflated (P = 0.003) and negative binomial (P = 0.045) model components (P , 0.001, n = 578). Conclusions: In those with migraine, severe photophobia is associated with reduced work productivity and higher presenteeism, absenteeism, activity impairment, and migraine-related disability. Journal of Neuro-Ophthalmology 2024;44:259–266 doi: 10.1097/WNO.0000000000001967 © 2023 by North American Neuro-Ophthalmology Society P hotosensitivity, most commonly called “photophobia” in the migraine literature, is reported in up to 93% of people with migraine during migraine attacks.1 Photophobia is the most commonly identified most bothersome migraine attack symptom other than headache.2 The presence and severity of photophobia correlates with the presence and severity of other migraine symptoms, such as headache intensity and phonosensitivity.3 Few studies have investigated the relationship between photophobia with migraine-related disability.4–8 Published studies have noted that high photosensitivity scores are significantly associated with the presence of missed activity time.8 It also has been shown that photophobia, phonophobia, and nausea independently predict worse functioning and quality of life.7 Although these few studies have demonstrated a relationship between photophobia and disability, there is a paucity of studies that have used a validated photophobia questionnaire to investigate whether photophobia severity is associated with work productivity, activity impairment, and migraine-related disability. This study used the Photosensitivity Assessment Questionnaire (PAQ), a 16-item validated questionnaire that evaluates photophobia and light-seeking behavior, to investigate a possible relationship between the severity of photophobia with work productivity and activity impairment (using the Work Productivity and Activity Impairment [WPAI] questionnaire) and migraine-related disability (using the Migraine Disability Assessment [MIDAS]).9–11 Our hypothesis was that severe photophobia would be positively associated with reduced work productivity, more activity impairment, and greater migraine disability. METHODS Design and Setting The American Registry for Migraine Research (ARMR) is a multicenter, prospective longitudinal patient registry comprised of patients with headache diagnosed according to the International Classification of Headache Disorders (ICHD-3) 260 criteria.2 Patients were recruited and enrolled from 9 ARMR sites, which were headache specialty clinics at Mayo Clinic Arizona, University of Utah, Georgetown University Medical Center, DENT Neurologic Institute, Dartmouth-Hitchcock Medical Center, University of Colorado, Thomas Jefferson University, University of Texas Health Science Center at Houston, and Yale University. The ARMR study had IRB approvals from each of the enrolling sites and all participants signed informed consent documents. ARMR contains a vast amount of patient data, including but not limited to, demographic information, headache features and characteristics, medical history, current treatments, and the impact of headache on life functioning. Patients within ARMR filled out a comprehensive baseline questionnaire and a shorter follow-up questionnaire every 3 months thereafter. ARMR patients were enrolled between February 1, 2016 and May 6, 2020 (N = 2,707). Inclusion and Exclusion Criteria To meet inclusion criteria for this analysis, patients had a migraine diagnosis, data on age and sex, baseline questionnaire data on headache frequency and headache intensity over the previous 90 days, and they completed MIDAS and PAQ questionnaires (N = 1,084). Of these included patients, those with data of WPAI questionnaire (N = 584), PHQ-2 (N = 584) and generalized anxiety disorder (GAD-7) data (N = 578) were included for analysis of presenteeism and absenteeism. Data Extraction Patient data extracted from the ARMR database included: basic demographics (age, sex, employment status), headache frequency (measured with the self-reported answer to the question: “Over the last 3 months, on average how many days PER MONTH did you have a headache of any type or some degree of headache? [Please specify, between 0 and 30]”), average headache intensity using a Numerical Rating Scale (NRS), Migraine Disability Assessment (MIDAS), Photosensitivity Assessment Questionnaire (PAQ), Work Productivity and Activity Impairment (WPAI), Patient Health Questionnaire (PHQ-2), and generalized anxiety disorder (GAD-7). Questionnaires The NRS is a widely used pain scale in which pain severity is rated from “no pain” (a score of 0) to having the “worst pain possible” (a score of 10).12 MIDAS quantifies headache-related disability over the previous 3-month period.9 It consists of 5 questions in which patients estimate the number of days within the past 3 months that their headaches had created substantial limitations or made them absent in work, household work, and social activities. MIDAS total scores of 0–5 indicate little or no disability, 6–10 indicate mild disability, 11–20 indicate moderate disability, and .20 indicate severe disability. WPAI measures work interference and the impairment of work and regular Leibovit-Reiben et al: J Neuro-Ophthalmol 2024; 44: 259-266 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Original Contribution FIG. 1. Relationship between photophobia and the transformed MIDAS score. The relationship of between photophobia (PAQ score) and the Transformed MIDAS score (after logarithmic transformation) are shown on this plot that contains a regression line with confidence intervals and prediction intervals. The confidence intervals and prediction intervals were generated using the mean values for the controlled variables of age, sex, headache frequency, average headache intensity, PHQ-2 scores and GAD-7 scores. The red highlighted area is the 95% confidence interval, and the blue area is the 95% prediction interval. GAD7 indicates generalized anxiety disorder; MIDAS, migraine disability assessment; PAQ, Photosensitivity Assessment Questionnaire; PHQ-2, patient health questionnaire. activities because of health problems.10 It consists of 6 questions that produce 4 different measures: absenteeism (percentage of work time missed because of illness), presenteeism (amount of productivity lost while working because of illness), nonwork activity impairment (amount of productivity lost while engaging in nonwork activity), and overall work productivity impairment (a composite measure that factors absenteeism and presenteeism). PAQ is a 16item validated questionnaire that evaluates photophobia and light-seeking behavior.11 In this analysis, only photophobia scores were included. Photophobia scores are calculated by the sum of its 8 items divided by the total number of items, where having no photophobia is a score of 0 and having the maximum amount of photophobia is a score of 1. Healthy controls in 2 Italian studies reported mean photophobia scores of 0.11 (SD 0.13) and 0.12 (SD 0.13).11 The GAD-7 is a valid and efficient tool that can screen for generalized anxiety disorder in the clinical and research setting.13 A score of 0–4 is interpreted as having no or minimal anxiety, 5–9 having mild anxiety, 10–14 having moderate anxiety, and 15–21 having severe anxiety. PHQ-2 is the first 2 items of the Patient Health Questionnaire-9 and Leibovit-Reiben et al: J Neuro-Ophthalmol 2024; 44: 259-266 screens for depression.14 Having a cutoff value of 2 is used to screen for any depressive disorder and a value of 3 meets the criteria for major depressive disorder (MDD). Statistical Analysis In this analysis, summary statistics are presented as means and standard deviations for variables that were normally distributed and as medians and interquartile ranges for variables that were not normally distributed. In the models, sexes reported as other than “female” were combined into one category because the number of participants reporting nonfemale sex was small. The scores of MIDAS, WPAI, PAQ, headache frequency, headache intensity, PHQ-2, and GAD-7 were used as continuous variables. Multiple linear regression models were developed to measure the relationships between photophobia and presenteeism, activity impairment, and overall work impairment. These regression models generated an adjusted R2, a P-value for the model, and a P-value for the predictor variable. To examine the relationship between photophobia and MIDAS scores, a logarithmic transformation of the MIDAS score was performed before model fitting because the MIDAS scores were not normally distributed. A zero261 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Original Contribution inflated negative binomial regression model was used to measure the relationship between photophobia and absenteeism, because the data were not normally distributed because of over half of the patients who completed the WPAI reporting no missed time from work because of headache. In all models, the following were entered as control variables: age, sex, headache frequency over the last 3 months, and average headache intensity over the last 3 months. In the MIDAS, overall work impairment, activity impairment, presenteeism, and absenteeism models, the PHQ-2 and GAD-7 scores were added as control variables because of the known association between depression and anxiety with migraine-related disability, absenteeism, and presenteeism.15,16 Sex was the only categorical variable within each of these analyses. There was no a priori power calculation performed, because the study was retrospective and all available data were included. Missing data were handled using pair-wise deletion. Data were analyzed using the R statistical computing program (version 3.2.2) and IBM SPSS Statistics for Windows (Version 28, NY). RESULTS Summary Statistics There was a total of 1,084 participants included in this analysis. Participant demographics and summary statistics for the questionnaire scores are shown in Table 1. Most patients in this analysis were women (n = 945; 87.2%). Population mean (SD) age was 46.1 (13.8) years (range: 18–86, n = 1,084), mean frequency of headache days over the last ninety-days was 44.3 (29.9) (n = 1,084), and mean headache intensity was 5.9 (1.7) (n = 1,084). The mean PAQ score was 0.47 (0.32) (n = 1,084). The median PHQ-2 score was 1 (IQR 0–2) (n = 584); where 36.3% (n = 212) had a score of 2 or higher meeting the screening criteria of having any depressive disorder on the PHQ-2 and 14% (n = 82) had a score of at least 3 or higher meeting the screening criteria for MDD. The median GAD-7 was 5 (2–8) (n = 578), where 49.8% (n = 291) of patients met the screening criteria for at least having mild anxiety, 9.2% (n = 53) having moderate anxiety, and 7.8% (n = 45) meeting the threshold for severe anxiety. The MIDAS score indicated severe migraine-related disability, because the median was 38 (IQR 15.0–80.0) (n = 1,084). Of these patients, 53.9% (584/1,084) were currently employed. Of these currently employed patients, 47.4% (n = 277) reported missing work in the past week because of migraine. Mean overall work impairment was 42.8% (26.7) (n = 584), mean activity impairment was 42.5% (26.2) (n = 584), mean presenteeism score was 38.4% (24.4) (n = 584), and the median absenteeism was 0 (IQR 0–14.5) (n = 584). TABLE 1. Summary statistics Questionnaire Age (y) Headache days (over last 3 mo) Average headache intensity (out of 10) PAQ score Overall work impairment (%) Activity impairment (%) Presenteeism (%) PHQ-2 GAD-7 MIDAS Absenteeism (%) Sex Number Completed Mean Standard Deviation 1,084 1,084 1,084 1,084 584 584 584 46.1 44.3 5.9 0.47 42.8 42.5 38.4 13.8 29.9 1.7 0.32 26.7 26.2 24.4 Median Interquartile Range 1 5 38 0 Percentage 945/1,084 87.2% female 136/1,084 12.5% male 3/1,084 0.30% unknown* 0–2 2–8 15–80 0–14.5 584 578 1,084 584 1,084 Results of each questionnaire, including the number of patients who completed the questionnaire, mean score, and standard deviation are included. The cutoff point on MIDAS for severe migraine-related disability is . 20. *There were 3 patients who did not disclose their sex and were labeled unknown. GAD-7, generalized anxiety disorder; MIDAS, migraine disability assessment; PAQ, photosensitivity assessment questionnaire; PHQ-2, patient health questionnaire. 262 Leibovit-Reiben et al: J Neuro-Ophthalmol 2024; 44: 259-266 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Original Contribution TABLE 2. Linear regression model for migraine disability assessment scores after logarithmic transformation Variable PAQ score Covariates Age Sex Headache days Average headache intensity PHQ-2 depression GAD-7 Estimate 95% CI Standard Error P 0.296 0.215 to 0.377 0.041 ,0.001 20.006 20.054 0.008 0.060 0.041 0.003 20.007 to 20.004 20.127 to 0.018 0.007 to 0.009 0.046 to 0.074 0.022 to 0.060 20.003 to 0.009 0.001 0.037 0.000 0.007 0.010 0.003 ,0.001 0.143 ,0.001 ,0.001 ,0.001 0.323 The effects of PAQ score, age, headache frequency, average headache intensity scores, and PHQ-2 were all statistically significant (P , 0.001). A total of 1,036 patients were included in this analysis. The P value for the model is ,0.001 and the adjusted R2 for the model is 0.461. Bolded text indicates significance with a P , 0.05. Estimates are unstandardized. PAQ was analyzed as an independent variable in each of the models. GAD-7, generalized anxiety disorder; PAQ, photosensitivity assessment questionnaire; PHQ-2, patient health questionnaire. Associations Between Photophobia Scores With Work Productivity and Impairment and Migraine-Associated Disability After controlling for age, sex, headache frequency, average headache intensity, and PHQ-2 and GAD-7 scores, there were statistically significant associations between photophobia scores with: a) MIDAS scores (F[7,1028] = 127.42, P , 0.001, R2 = 0.461, n = 1,036) (Table 2 and Fig. 1); b) overall work impairment (F[7,570] = 29.23, P , 0.001, R2 = 0.255, n = 578) (Table 3); c) activity impairment (F[7,570] = 27.42, P , 0.001, R2 = 0.243, n = 578) (Table 3); d) and presenteeism (F[7,570] = 29.17, P , 0.001, R2 = 0.255, n=578) (Table 4). Across all models, the maximum variance inflation factor was 1.67, indicating the variances of the coefficient estimates were not substantially affected by multicollinearity. A zero-inflated negative binomial model has 2 components; the first component describes the probability of a zero response (no missed work time) and the negative binomial component, which in our case describes the number of hours missed for those who did not have a zero response in the first part. Overall, the presence of photophobia in the absenteeism model contributed significantly as assessed with a chi-squared likelihood ratio test (P = 0.001, df = 17) (Table 5). There was a statistically significant association between photophobia TABLE 3. Linear regression models for overall work impairment and activity impairment scores Variable Overall work impairment PAQ score Covariates Age Sex Headache days Average headache intensity PHQ-2 depression GAD-7 Activity impairment PAQ score Covariates Age Sex Headache days Average headache intensity PHQ-2 depression GAD-7 Estimate 95% CI Standard Error P 11.489 4.974 to 18.004 3.317 ,0.001 20.103 22.050 0.289 4.440 2.098 20.001 20.272 to 0.066 28.090 to 3.991 0.220 to 0.358 3.279 to 5.601 0.438 to 3.759 20.501 to 0.500 0.086 3.075 0.035 0.591 0.846 0.255 0.231 0.505 ,0.001 ,0.001 0.013 0.998 12.419 5.983 to 18.854 3.276 ,0.001 20.046 27.652 0.244 4.008 2.511 0.000 20.213 to 0.121 213.619 to 21.685 0.175 to 0.312 2.860 to 5.155 0.871 to 4.152 20.494 to 0.494 0.085 3.038 0.035 0.584 0.835 0.252 0.586 0.012 ,0.001 ,0.001 0.003 0.999 The effects of PAQ score, headache frequency, and average headache intensity scores were all statistically significant (P , 0.001). The additional effect of PHQ-2 was statistically significant (P = 0.013, P = 0.003) for the overall work impairment and activity impairment models. Sex was only statistically significant (P = 0.012) in the activity impairment model. A total of 578 patients were included in this analysis. The P values for the overall work impairment and activity impairment models are ,0.001. The adjusted R2 for the overall work impairment model is 0.255. The adjusted R2 for the activity impairment model is 0.243. Bolded text indicates significance with a P , 0.05. GAD-7, generalized anxiety disorder; PAQ, photosensitivity assessment questionnaire; PHQ-2, patient health questionnaire. Leibovit-Reiben et al: J Neuro-Ophthalmol 2024; 44: 259-266 263 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Original Contribution TABLE 4. Linear regression model for presenteeism scores Variable PAQ score Covariates Age Sex Headache days Average headache intensity PHQ-2 depression GAD-7 Estimate 95% CI Standard Error P 8.758 2.797 to 14.718 3.035 0.004 20.099 22.377 0.240 4.204 2.314 0.110 20.254 to 0.056 27.903 to 3.150 0.177 to 0.303 3.141 to 5.266 0.795 to 3.834 20.348 to 0.567 0.079 2.814 0.032 0.541 0.774 0.233 0.210 0.399 ,0.001 ,0.001 0.003 0.638 The effects of PAQ score, headache frequency, average headache intensity, and PHQ-2 scores were all statistically significant (P = 0.004, P , 0.001, P , 0.001, P = 0.003). A total of 578 patients were included in this analysis. The P value for the model is ,0.001 and the adjusted R2 for the model is 0.255. Bolded text indicates significance with a P , 0.05. GAD-7, generalized anxiety disorder; PAQ, Photosensitivity Assessment Questionnaire; PHQ-2, Patient Health Questionnaire. scores and absenteeism for the zero-inflated (P = 0.003) and negative binomial (P = 0.045) components. DISCUSSION The results of this analysis demonstrate an association between the severity of photophobia and reduced work productivity, higher presenteeism, more overall work impairment, greater activity impairment, and more absenteeism and higher migraine-related disability. These results highlight that photophobia, the most commonly identified, most bothersome nonheadache symptom, independently from headache features, depression and anxiety, worsens migraine-related disability and functioning. This analysis supports, and expands on, the few previous studies that have investigated the relationship between photophobia with disability and functioning among those with migraine.4–8 In our analysis, we controlled for number of headache days and average headache pain intensity when measuring the association between photophobia with disability and functioning. Headache frequency and average headache pain intensity are known to impact migraine-related disability and have been demonstrated to account for up to 19.9% of the variance in MIDAS scores.17 In addition, an increase in 1 headache-free day was associated with a decrease in WPAI absenteeism, presenteeism, activity impairment, and total work impairment.18 Our results demonstrate that photophobia severity is associated with higher disability scores and worse functioning, independent from these other headache features. TABLE 5. Zero-inflated negative binomial regression model for absenteeism Variable Zero-inflated PAQ score Age Sex Headache days Average headache intensity PHQ-2 depression GAD-7 Negative binomial PAQ score Age Sex Headache days Average headache intensity PHQ-2 depression GAD-7 Estimate 95% CI Standard Error P 20.945 0.013 0.189 20.014 20.169 20.008 0.002 21.529 to 20.276 20.003 to 0.029 20.412 to 0.84 20.02 to 20.007 20.279 to 20.055 20.157 to 0.146 20.049 to 0.051 0.312 0.008 0.290 0.003 0.057 0.078 0.024 0.003 0.115 0.515 ,0.001 0.003 0.914 0.945 0.391 0.004 20.057 0.008 0.117 0.085 20.021 20.051 to 0.804 20.007 to 0.015 20.582 to 0.556 0.003 to 0.011 0.036 to 0.192 20.009 to 0.189 20.051 to 0.01 0.195 0.005 0.199 0.002 0.038 0.041 0.014 0.045 0.476 0.775 ,0.001 0.002 0.039 0.141 The effects of PAQ score, headache frequency, and average headache intensity scores were all statistically significant for zero inflated (P = 0.003, P , 0.001, P = 0.003) and negative binomial (P = 0.045, P , 0.001, P = 0.002) components. The effect of PHQ-2 was only significant in the negative binomial component (P = 0.039). A total of 578 patients were included in this analysis. Bolded text indicates significance with a P , 0.05. The chi-square likelihood ratio test showed the model with photophobia was significantly better than the model without (P = 0.001). GAD-7, generalized anxiety disorder; PAQ, Photosensitivity Assessment Questionnaire; PHQ-2, Patient Health Questionnaire. 264 Leibovit-Reiben et al: J Neuro-Ophthalmol 2024; 44: 259-266 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Original Contribution Depression and anxiety are important variables that impact work presenteeism and absenteeism and migrainerelated disability.15,16 Previous studies have shown that individuals with chronic photophobia have higher anxiety and depression.19 Because anxiety and depression may affect working and disability, they were included as covariates in all models. The results of our study extend on the findings of previous studies that have explored the association between photophobia with disability and functioning. In a crosssectional study including 187 patients with migraine, it was found that patients with 3 sensory hypersensitivities (photophobia/phonophobia/osmophobia) compared with 0–2 sensory hypersensitivity symptoms had higher MIDAS scores.4 Our results add to that study, demonstrating that the single hypersensitivity, photophobia, is positively associated with higher migraine-related disability. Our results contradict those of a study that included 46 individuals who had episodic migraine without aura, in which self-reported sensory hypersensitivities (light/sound/odor) did not correlate with migraine disability measured with MIDAS and the Headache Impact Test (HIT-6).5 A study of 92 patients with migraine investigated the relationship between headache characteristics with disability measured on a daily basis, using 422 days of diary data. Although the presence of selfreported photophobia was significantly associated with disability (r = 0.244, P , 0.05), it was not a significant factor predicting disability in regression analysis (P = 0.055).6 In line with our findings, a study that included 232 individuals with migraine found that the severity of photophobia, phonophobia, and nausea each measured using a 4-point scale (0 = none; 3 = severe) were independent predictors of migraine-associated disability measured with MIDAS.7 Our study extends on these previous findings regarding the relationship between photophobia and migraineassociated disability by including a large sample size, measuring the impact of photophobia alone, measuring the severity of photophobia instead of just its presence or absence, and using a validated questionnaire for assessing photophobia severity. In addition, our results demonstrate the association between missed activity time and photophobia. Results are consistent with a study of 37 adolescents with migraine, in which having higher combined photophobia and phonophobia sensitivity scores (0; not present; 1, at least one present; 2, both present) was associated with increased likelihood of recording missed activity hours (defined as hours of missed school, work, and extracurricular or social activities).8 Our results emphasize that photophobia severity can be thought of as an independent predictor for reduced work productivity, missed activity time, and more activity impairment. In addition, our findings suggest that photophobia contributes to time absent from work among those employed. Our findings suggest that photophobia may be Leibovit-Reiben et al: J Neuro-Ophthalmol 2024; 44: 259-266 more disabling than previously suggested in some literature.5 Limitations of our study include: 1) Although the PAQ is a validated questionnaire, it was not specifically designed to assess light sensitivity attributed to migraine. Since the development of ARMR, there have been newly validated photophobia questionnaires that may more comprehensively measure photophobia in those with migraine.20 2) Because the PAQ was not specifically designed to assess photophobia associated with migraine, the questionnaire assesses overall measures of photophobia, without differentiating between photophobia occurring during migraine attacks vs interictally. 3) Our results may not be generalizable to the larger population of people with migraine because the patients in ARMR are enrolled from headache specialty clinics. Conclusions More severe photophobia in migraine patients is associated with reduced work productivity and higher presenteeism, absenteeism, activity impairment, and migraine-related disability. The results of this study highlight that photophobia, which is the most commonly identified, most bothersome nonheadache symptom, independently worsens migraine-related disability and functional impairment. STATEMENT OF AUTHORSHIP Conception and design: Z. Leibovit-Reiben, G. Dumkrieger, D. W. Dodick, K. Digre, C. D. Chong, M. Trivedi, T. J. Schwedt; Acquisition of data: Z. Leibovit-Reiben, G. Dumkrieger, D. W. Dodick, C. D. Chong, T. J. Schwedt; Analysis and interpretation of data: Z. LeibovitReiben, G. Dumkrieger, T. J. Schwedt. Drafting the manuscript: Z. Leibovit-Reiben, T. J. Schwedt; Revising the manuscript for intellectual content: Z. Leibovit-Reiben, G. Dumkrieger, D. W. Dodick, K. Digre, C. D. Chong, T. J. Schwedt. Final approval of the completed manuscript: Z. Leibovit-Reiben, G. Dumkrieger, D. W. Dodick, K. Digre, C. D. Chong, M. Trivedi, T. J. Schwedt. ACKNOWLEDGMENTS The authors gratefully acknowledge the American Registry for Migraine Research (ARMR) for the use of registry data to conduct this research, and thank the patients and clinicians who participated in this registry. REFERENCES 1. Renjith V, Pai MS, Castelino F, Pai A, George A. 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