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FEATURE ARTICLE — PUBLIC ACCESS

Photophobia Associated with Traumatic Brain Injury: A Systematic Review and Meta-analysis

Merezhinskaya, Natalya PhD1; Mallia, Rita K. OD, MPA1; Park, DoHwan PhD2; Millian-Morell, Lymarie PhD1; Barker, Felix M. II OD, MS, FAAO1∗

Author Information
Optometry and Vision Science: August 2021 - Volume 98 - Issue 8 - p 891-900
doi: 10.1097/OPX.0000000000001757

Abstract

Traumatic brain injury is defined as a disruption in the normal function of the brain that can be caused by a bump, blow, or jolt to the head, as well as due to a penetrating head injury.1 Traumatic brain injury is a significant public health problem: there were approximately 2.87 million combined traumatic brain injury–related emergency department visits, hospitalizations, and deaths in the United States in 2014.2 From 2000 to 2019, 417,503 U.S. military personnel have been diagnosed with traumatic brain injury.3 Traumatic brain injury is often associated with physical, sensory, and cognitive symptoms and dysfunctions, including those affecting the visual system. A recent systematic review and meta-analysis showed that the prevalences of accommodative dysfunction, convergence insufficiency, and visual field loss in patients with traumatic brain injury without concomitant eye injury were 42.8% (95% confidence interval, 31.3 to 54.7%), 36.3% (95% confidence interval, 28.2 to 44.9%), and 18.2% (95% confidence interval, 10.6 to 27.1%), respectively, with no significant loss of visual acuity.4 Another reported symptom of traumatic brain injury is photophobia (also sometimes referred to as light sensitivity), a state of discomfort or pain in response to light that may also cause light avoidance.5–7 Currently, there are no validated objective tools to quantify photophobia. Therefore, the presence of photophobia is determined almost exclusively by clinical history from patient self-report or questionnaires. Consequently, the reported frequency of photophobia varies substantially across studies.

The purpose of this study was to perform a systematic review and meta-analysis of the literature to report the prevalence of photophobia in patients with traumatic brain injury as a function of time after the injury. We also performed multivariate meta-regression analysis to account for observed heterogeneity over time, target population, photophobia assessment tools, study design (retrospective vs. perspective), and risk of bias as moderators. Lastly, we assessed the risk ratio for having photophobia in traumatic brain injury versus control subjects over time.

METHODS

Systematic Literature Search

Three databases (PubMed, EMBASE, and Cochrane Library) were queried individually for literature published before September 2019 regarding photophobia in patients with traumatic brain injury. Two search strategies using slightly different terms and/or search strings were adapted for the three databases. Appendix Table A1, available at https://links.lww.com/OPX/A509, describes the complete search strategies used. Briefly, search strings were organized into three concepts: (1) head injury, (2) photophobia, and (3) topic/scope. Terms within each category were separated by the Boolean operator “OR,” and each category was parenthesized and separated by the operator “AND.” When possible, Medical Subject Heading terms or the “explode” qualifier was used to expand the search language. References and citations were managed using EndNote X8.2 (Clarivate, Philadelphia, PA). All references deemed appropriate for inclusion were manually screened for relevant literature; this step was conducive to finding studies in which photophobia was not the primary experimental focus. Systematic and narrative reviews were also inspected for additional studies.5–14

Inclusion and Exclusion Criteria

To be considered for inclusion, studies were required to (1) report a sample of patients with traumatic brain injury or concussion confirmed by a qualified professional (e.g., physician, neurologist, certified athletic trainer) using acceptable diagnostic criteria such as Glasgow Coma Scale or comparable metric; (2) evaluate all patients with traumatic brain injury for photophobia no later than 12 months after they sustained an initial traumatic brain injury diagnosis using objective criteria, patient self-reports, or clinical surveys/questionnaires; and (3) be an original peer-reviewed work in English.

A study was excluded if (1) the brain injury was reported by the patients themselves or parent/guardian; (2) brain injuries had a nontraumatic source (e.g., ischemia, stroke); (3) symptoms of photophobia were explicitly attributed to a nontraumatic brain injury etiology (e.g., uveitis, dry eye, eye trauma); (4) patients had a history of headaches, including migraines, or post-traumatic stress disorder before diagnosis of traumatic brain injury; (5) photophobia was only evaluated at more than 12 months after the traumatic brain injury; or (6) the study was a case report. If two or more studies reported data on overlapping cohorts for the same time frame, either the larger cohort or the most recent study was included; however, if two or more studies provided data on the same cohort but for different time frames, then both studies were included.

Data Extraction

Prevalence estimates of photophobia in traumatic brain injury or control patients were extracted directly from data tables, figures, or text. Patients were considered photophobic if they reported any level of light sensitivity after the injury. When available, additional contextual data extracted from each study included the following: geographic location (country) of the study, age, sex (or participants sex ratio), target population (i.e., defining characteristics of the recruited population), time since traumatic brain injury, traumatic brain injury severity, study design (retrospective or prospective), photophobia assessment tool, causes of traumatic brain injury (i.e., mechanism of injury), and risk of bias; the same data were extracted for control patients when available.

Methodological Quality Appraisal

Methodological quality assessment was performed to appraise individual studies. We used the criteria validated by Munn et al.,15 designed to assess the quality of studies reporting prevalence data. Individual criteria are provided in Appendix Table A2, available at https://links.lww.com/OPX/A510, with minor alterations to fit the current research question. A criterion was considered “no” if the standard was not met or the relevant portion of the study was unclear. Each study was appraised by two of the authors (RKM and LM-M); discordant ratings were assessed by a third author (NM).

Statistical Data Analysis

Statistical analyses were performed using R statistical software (3.6.2)16 and the associated “meta” and “metafor” packages.17 The photophobia prevalence rates were calculated as a percentage of patients with traumatic brain injury and with photophobia of the total number of patients with traumatic brain injury at various time intervals after traumatic brain injury specified in each report; in instances where prevalence estimates were equal to 0.0, a continuity correction of 0.5 was applied.18

Several studies reported rates of post-traumatic photophobia at multiple time points for traumatic brain injury and control groups (e.g., initial and follow-up assessments)19–45; in these cases, a series of meta-regression analyses was performed using the generalized linear mixed model to account for heterogeneity in the prevalence of photophobia as a function of time since traumatic brain injury. For the analysis of traumatic brain injury studies, we extracted data for the prevalence of photophobia with associated time since traumatic brain injury from both multiple-time and single-time encounters from 75 studies, which yielded a total of 119 data points. To account for heterogeneity in the prevalence of photophobia between studies, we conducted a meta-regression using a logit-link logistic model. Prevalence rates were transformed using the logit-transformed proportion, logit(P) = log(odds) = log(P/(1 − P)) and used as average effect. Weights for each study were calculated using the inverse variance of transformed proportions, but tables are presented with back-transformed data (i.e., raw prevalence). The pre-specified moderators included in the meta-regression were as follows: time since traumatic brain injury, risk of bias, target population (general, pediatric, sport, and military), study design (prospective, retrospective), and testing (graded, yes/no, not reported). Dummy variables were used for regression analyses of all moderators except time since traumatic brain injury. Time since traumatic brain injury was modeled as a continuous variable between 0 and 12 months. Several models were considered (see the details in Appendix Table A3, available at https://links.lww.com/OPX/A511). In brief, we first used a full generalized linear mixed model with all potential moderators and random effects. Subsequently, a backward elimination model selection procedure was used in which the least significant moderators were eliminated and only moderators with significant effects were considered. Because time was found to be a significant moderator, a linear spline model of time after traumatic brain injury with a random-effects analysis of these studies was used. Because of the rapidly decreasing trend at earlier post-traumatic brain injury times, we used different linear trend models for the periods of 0 to 3 months versus 3 to 12 months. Variances across studies were combined using the DerSimonian and Laird46 random-effects model because of a high propensity for statistical heterogeneity; variance between studies (τ2) was estimated by the restricted maximum likelihood method to accommodate meta-regression analyses. Statistical heterogeneity was assessed with Cochran Q and Higgins I2; I2 values <40%, between 30 and 60%, between 50 and 90%, and ≥75% were considered low, moderate, substantial, and considerable heterogeneity, respectively. Heterogeneity estimates were determined to be statistically significant at P < .10, because Cochran Q has demonstrated low power under many circumstances.47 Confidence intervals at the 95% level were estimated according to Clopper and Pearson.48 Among 75 studies that reported time since traumatic brain injury, 14 publications compared the photophobia prevalence with a control population. The prevalence adjusted for the time since traumatic brain injury in both control and traumatic brain injury groups was modeled by generalized linear mixed model. Because of the limitation imposed by the small number of studies, we used a time continuous model for the analysis. Because our analysis indicated that the prevalence of photophobia in the control group remains constant, we used a model with an interaction term that allowed for a different rate of change for the two groups over time: time continuous for the traumatic brain injury group and time constant for the control group (Appendix Table A3, available at https://links.lww.com/OPX/A511). The relative risk for time-adjusted prevalence rate was calculated by dividing the estimated photophobia rate of traumatic brain injury by the estimated photophobia rate of the control group from the generalized linear mixed model. The Delta method was used to estimate the standard error of the risk ratio.

RESULTS

Search Results

Database queries yielded 6588 unique studies; of these, 5591 were excluded primarily because quantifiable data regarding photophobia were not reported. Other exclusionary parameters included nontraumatic brain injury sample, studies with overlapping cohorts for the same time points, traumatic brain injury reported by a patient/parent/guardian, time since traumatic brain injury greater than 12 months, single case reports, and photophobia symptoms that were conflated with other visual symptoms and/or noise sensitivity (e.g., reported frequency of “light/noise sensitivity” or “photophobia/visual symptoms”). After review of the titles, abstracts, and full texts, 75 articles met the criteria for inclusion.19–45,49–96 The systematic literature search strategy is depicted in Fig. 1 and followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines.97

FIGURE 1
FIGURE 1:
Flow diagram of the systematic literature review search process according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses.97 EMBASE = Excerpta Medica Database; TBI = traumatic brain injury.

Study Characteristics

Descriptive characteristics of the 75 studies can be found in Appendix Table A4, available at https://links.lww.com/OPX/A512. More than half were conducted in the United States or by Americans at foreign military bases (n = 41; 55%); Australian and New Zealand studies were the next most common (n = 11; 15%), followed by Canadian studies (n = 10; 13%). Countries in Europe and Asia were also represented. Participants were most often recruited from hospital catchment areas and therefore were sampled from the general traumatic brain injury population. However, additional population categories included sports injuries,32,34,51,57–59,61,63–66,76–78,80,95 military service members and veterans,24,40,73,91 and pediatric cases.21,50,53,54,60,62,68,71,81,88,90 Causes of injury included sports injuries, motor vehicle accidents, falls, assaults, and explosive blast. Assessment of photophobia was performed almost entirely by a survey or questionnaire; although many studies used evaluation tools not commonly or widely used, the well-established Rivermead Post-concussion Symptoms Questionnaire was common (n = 24; 32%). Fourteen studies had prevalence data in both traumatic brain injury and control groups with indicated period since traumatic brain injury.22,23,28,31,39,43,52,53,55,68,72,79,85,88 Methodological quality of the studies ranged from low to high risk of bias: 84% of the studies were low risk of bias, 16% were moderate risk of bias, and 0% were high risk of bias (Appendix Table A5, available at https://links.lww.com/OPX/A513). A majority of the studies were prospective (75%) versus retrospective (25%).

Prevalence of Photophobia in Patients with Traumatic Brain Injury

Our meta-regression analysis used data from 75 publications with a total number of 27,942 individuals with traumatic brain injury, 7794 of whom had photophobia. Approximately 60% were cross-sectional studies, and the remaining 40% contained multiple prevalence rate measurements (2 to 4), resulting in 119 data points from 75 studies. The reported prevalence of photophobia ranged from 023 to 81.8%,59 which is considerably heterogeneous. It was hypothesized that the interval between sustaining a traumatic brain injury and being evaluated for photophobia (i.e., time since traumatic brain injury) would impact the reported prevalence in the included studies.

Fig. 2 shows the prevalence of photophobia in four different population groups (general, pediatric, sports, and military) as a function of time. The sports-injured population had the largest number of individuals (14,731 individuals with 5435 photophobia events from 17 publications) followed by general traumatic brain injury cases (10,541 individuals and 1471 events from 43 publications), pediatrics (1966 individuals and 592 events from 11 publications), and military (704 individuals and 296 events from four publications).

FIGURE 2
FIGURE 2:
Prevalence of photophobia as a function of time in different populations. Dotted lines represent studies with follow-ups; individual markers represent single-time-point studies.

For all populations except military, there was a decrease in photophobia prevalence with the increase of time since injury, with a more rapid decline during the first 3 months followed by a leveling off between 3 and 12 months after traumatic brain injury. The period immediately after the injury up to 3 months was represented by all populations; however, the 3- to 12-month period was represented almost exclusively by the general population (Appendix Table A6, available at https://links.lww.com/OPX/A514).

Studies (or cohorts within a study) were stratified into the following discrete time categories to determine the prevalence of photophobia: ≤1 week, >1 week to ≤1 month, >1 to ≤3 months, >3 to ≤6 months, and >6 to ≤12 months since traumatic brain injury. When a cohort's time since traumatic brain injury was reported as a range of times within the same time category, the mean of the data points was used. The results are shown in Table 1. The stratified prevalence of photophobia was the highest within 1 week (30.46%), decreasing between 1 week and 1 month (19.34%), and further to its lowest rate between 1 and 3 months after traumatic brain injury (13.51%). This decrease was followed by a slight increase between 3 and 6 months (17.68%) and again a slight decrease between 6 and 12 months (14.85%).

TABLE 1 - Prevalence of photophobia in the TBI group at different times since injury intervals
Time (intervals) Prevalence (%) 95% CI (%)
0–1 wk 30.46 20.05–40.88
1 wk–1 mo 19.34 10.40–28.27
1–3 mo 13.51 5.77–21.24
3–6 mo 17.68 9.05–26.32
6–12 mo 14.85 6.80–22.90
CI = confidence interval; TBI = traumatic brain injury.

The estimated overall prevalence of photophobia as a function of time based on the linear spline model with generalized linear mixed model is shown in Fig. 3, with the total sample size of individual studies represented as circles. This model-based analysis demonstrated a decrease in the prevalence of photophobia from the initial injury up to 3 months after the injury, with a slight uptick from 3 to 12 months. Whereas the initial decrease from 0 to 3 months was statistically significant (odds ratio, 0.74; P < .001), the later slight increase from 3 to 12 months was negligible (odds ratio, 1.03; P = .02; Appendix Table A7, available at https://links.lww.com/OPX/A515).

FIGURE 3
FIGURE 3:
Estimated prevalence of photophobia as a function of time. Solid line represents the estimated prevalence, and dotted lines represent 95% confidence interval. The circles are actual data, with the size of the circle corresponding to the sample size.

Our meta-regression analysis indicated that military and sports populations exhibit a higher prevalence of photophobia after a traumatic brain injury compared with the general population (military: odds ratio, 5.08 [95% confidence interval, 1.90 to 13.55; P < .001]; sports: odds ratio, 2.01 [95% confidence interval, 1.13 to 3.58; P = .02]), with the pediatric population approaching but not reaching significance with an odds ratio of 1.87 (95% confidence interval, 0.98 to 3.54; P = .06). In addition, the prevalence calculated based on the data from the retrospective study design was lower than the one based on the prospective study design (odds ratio, 0.52 [95% confidence interval, 0.29 to 0.93; P = .03]). Risk of bias and the type of testing/questionnaire were nonsignificant moderators (not shown).

Risk of Photophobia in Traumatic Brain Injury versus Control Populations

Of 75 studies, we used 14 publications that contained data for matched traumatic brain injury and control groups for a comparison measure of photophobia prevalence after traumatic brain injury. The total sample size for the traumatic brain injury group consisted of 2084 individuals, including 615 with photophobia, and the total sample size for the control group was 2233 individuals, including 153 with photophobia.

The control group is characterized in Appendix Table A4, available at https://links.lww.com/OPX/A512, and it included presumed healthy individuals22,23,31,39,43,52,72,79,85,88 and patients with soft tissue injuries, fractures, and/or lacerations of the extremities but without head and/or concussive injuries or symptoms, and/or mild traumatic brain injury.28,53,55,68 Our analysis indicated that there was no change in the prevalence of photophobia in the control group over time (not shown). For the corresponding traumatic brain injury group from the 14 studies, the estimated photophobia prevalence decreased as time increased (P < .001; Appendix Table A8, available at https://links.lww.com/OPX/A516). This finding was in agreement with the analysis based on the data from all 75 studies. The time-adjusted prevalence was significantly higher for the traumatic brain injury group than for the control group (odds ratio, 5.75 [95% confidence interval, 4.66 to 7.10; P < .001]).

To assess the risk of experiencing photophobia after traumatic brain injury, the risk ratio was calculated for patients with traumatic brain injury and control patients. The risk ratio estimates and 95% confidence intervals were greater than 1 at all times between 0 and 12 months, indicating that the traumatic brain injury group had a higher risk of having photophobia compared with the control population for up to 12 months since injury (Fig. 4).

FIGURE 4
FIGURE 4:
Estimated risk ratio of developing photophobia in patients with TBI compared with patients without TBI as a function of time. Dotted line represents 95% CI. CI = confidence interval; TBI = traumatic brain injury.

DISCUSSION

This study provides prevalence estimates of photophobia over time after a traumatic brain injury event. Photophobia prevalence was the highest within the first week after traumatic brain injury (30.46%; 95% confidence interval, 20.05 to 40.88%) followed by a significant steady decline up until 3 months (13.51%; 95% confidence interval, 5.77 to 21.24%; P < .001; Table 1). From 3 to 12 months, the prevalence of photophobia approached a steady state with a slight, nonsignificant increase of the prevalence between 3 and 6 months and a slight, nonsignificant decrease between 6 and 12 months. The periods from the time of injury to 6 months and at 12 months were well represented by the data; however, data were more limited for the period from 6 to 12 months, which likely contributed to observed fluctuations of the steady state during this interval (Fig. 3). These data provide evidence that a substantial number of affected individuals recover within 3 months after traumatic brain injury; however, those patients who are experiencing photophobia after 3 months may be entering a chronic phase lasting at least 12 months after the injury and possibly even longer.13,98 The same pattern was reported by Ponsford et al.,99 who looked at the sensory and neuropsychological outcomes in adults with mild traumatic brain injury at 1 week and 3 months after the injury. At 3 months after the injury, a majority of the symptoms reported at 1 week were largely resolved. However, in a subgroup of 24% of participants, many of the symptoms persisted and were implicated in the disruption of normal life activities. This observation further supports the notion that the recovery from photophobia, as with other post-traumatic brain injury visual symptoms, is a heterogeneous process that likely depends on the complexity and severity of the underlying traumatic brain injury, including focal versus diffuse injury and primary versus secondary traumatic brain injury effects.100,101

Elucidation of neural pathways involved in photophobia will further advance our understanding of the nature of this complex phenomenon and may point to better treatments. A recent publication by Diel et al.102 suggested a trigeminothalamic pathophysiology as a pathway of photophobia, as this condition is seen in patients with dry eye, migraine, and/or traumatic brain injury. Furthermore, inflammatory response has been suggested as one of the possible underlying mechanisms of these conditions by causing local overstimulation of neuronal activity. Interestingly, in animal studies of the effects of blast-mediated traumatic brain injury on retina and optic nerve integrity, both histological evaluation of oxidative stress, neuroinflammation, and cell death markers and functional changes measured by electroretinogram and pattern electroretinogram displayed acute and chronic time course similar to the one seen in this study.103,104

We were also interested in assessing moderators other than time concerning their potential contribution to the heterogeneity of the data. We performed multiple meta-regression analyses for the various populations reported (e.g., military, sports, pediatric, and general), study design (e.g., retrospective vs. prospective), risk of bias, and photophobia assessment tool (type of testing, questionnaire) as moderators. Our analyses indicated that military and sports populations had a significantly higher prevalence of photophobia after traumatic brain injury compared with the general population. In contrast, the pediatric population approached but did not reach significance as compared with the general population. The photophobia prevalence after traumatic brain injury for the military population was the highest and did not seem to diminish with time in contrast to other populations after traumatic brain injury (Fig. 2). This statement should be taken with caution because only four publications with a military population met our inclusion/exclusion criteria,24,40,73,91 and only Capo-Aponte et al.24 had data on longer-term photophobia prevalence. Several factors may explain why the military service members seemed to experience more severe and/or prolonged light sensitivity after traumatic brain injury. These individuals often acquire brain trauma as a result of a blast event, which is thought to have a greater impact than focal traumatic brain injuries from accidents or sport concussion among the civilian population. Magone et al.98 reported that 55% of military service members with blast-induced mild traumatic brain injury had light sensitivity that ranged from mild to moderate, more than 12 months after traumatic brain injury. Another factor that is important to the military traumatic brain injury population is polytrauma, which often necessitates multiple long-term medications, many of which can induce photophobia as an adverse effect.105,106 Post-traumatic stress disorder, a relatively common diagnosis in military service members after a traumatic brain injury event, has been independently associated with increased sensory sensitivity, including light sensitivity.14,107

The type of the study (retrospective vs. prospective) was the only other moderator that affected the photophobia prevalence. The prevalence based on data from the retrospective studies' design was significantly lower than that based on the prospective study design (P = .03), which may be a reflection of intent bias on the part of the investigators, although the moderators' risk of bias and the type of testing/questionnaire did not demonstrate significance. We could not assess other potential important moderators, such as traumatic brain injury severity, blast versus nonblast traumatic brain injury etiology, and effect of comorbidities (e.g., migraine and/or post-traumatic stress disorder), because of the lack of available data and/or an overlap of different cohorts in the reports.

Fourteen studies included data from matched patients with traumatic brain injury versus controls without traumatic brain injury, which allowed for the comparison of the time-dependent prevalence of photophobia between these two groups. The controls without traumatic brain injury comprised healthy individuals, patients without head trauma diagnoses, and orthopedic patients. Our preliminary analyses showed that the nature of the control group did not influence the results (not shown). Therefore, we used a combined control data set for further analyses. In agreement with the data based on all 75 publications, the estimated prevalence of photophobia in patients with traumatic brain injury from these 14 matched studies decreased with time after the traumatic brain injury event, and this decrease was highly statistically significant (P < .001; Appendix Table A6, available at https://links.lww.com/OPX/A514). In contrast, the prevalence of photophobia in the control group remained unchanged over time. The time-adjusted photophobia prevalence was significantly higher for the traumatic brain injury group compared with the control group (odds ratio, 5.75 [95% confidence interval, 4.66 to 7.10; P < .001]; Appendix Table A7, available at https://links.lww.com/OPX/A515).

Risk ratio (i.e., relative risk) estimation allows for mitigation of some of the statistical heterogeneity of the data by calculating the probability of the event (photophobia) in exposed (traumatic brain injury) versus nonexposed (without traumatic brain injury) cohorts. The estimated risk ratio showed that, immediately after traumatic brain injury, patients are at more than four times greater risk of experiencing photophobia than control patients without traumatic brain injury. The risk of having post-traumatic brain injury photophobia decreases with time, but patients with traumatic brain injury remain twice as likely as control patients to have photophobia at 12 months after the traumatic event (Fig. 4), suggesting that chronic photophobia may last longer than a year.

Considerations and Limitations

The subjective nature of the assessment and reporting of photophobia was one of the major limitations of this study, and it likely contributed to the high statistical heterogeneity among the studies.

Currently, there is no clinically available and approved instrument and no validated protocol to quantify photophobia. A recent study by Yuhas et al.108 demonstrated that grading light aversion behavior (blinking, tearing, and squinting) using video recordings failed to discriminate between post-traumatic brain injury photophobic and control cohorts. The authors emphasized the need for an objective test for diagnosing and managing photophobia.

Recently, several publications have described the development of an automated instrument to measure photosensitivity thresholds.109,110 However, at present, the limited number of available published quantitative studies relied on unique laboratory instrument setups that are not typical in a clinical setting, thus making data comparison and generalization from these data difficult. Consequently, photophobia is currently diagnosed almost exclusively based on patients' self-reports or clinical questionnaires. Many studies, including those in this analysis, used nonstandard or proprietary questionnaires. In many instances, specific photophobia questions were limited to a simple yes/no answer.

A few questionnaires did compare both the presence and severity of photophobia before and after injury to account for symptom changes; these questionnaires include commonly used post-concussion symptom assessment tools, such as the Rivermead Post-concussion Symptoms Questionnaire and the Neurobehavioral Symptom Inventory. The Rivermead Post-concussion Symptoms Questionnaire used measures to reduce bias and collect information on the impact of each symptom by directing patients to compare symptom severity before sustaining a traumatic brain injury with time points after the injury. Similarly, the Neurobehavioral Symptom Inventory requires that the patient consider only current photophobia severity in comparison with photophobia 2 weeks before photophobia during the last evaluation. Despite their advantages over other survey tools, neither the Rivermead Post-concussion Symptoms Questionnaire nor the Neurobehavioral Symptom Inventory provides an in-depth assessment of the photophobic symptoms, mainly because most questionnaires are not dedicated specifically to photophobia assessment and the questions about photophobia are incidental to their main focus. Several photophobia-dedicated questionnaires have been developed and used in published literature.110–112 However, they have not been formally accepted as validated tools.

Another limitation of this study is a possibility that some of the reported photophobia was secondary to conditions other than traumatic brain injury. We excluded studies reporting photophobia associated with non–traumatic brain injury conditions from this analysis. However, we cannot completely eliminate the possibility that some confounding factors (such as medications, pre-existing photophobia, etc.) had at least some impact on the data reported in this retrospective analysis.

In addition, the absence of well-defined data did not allow for a meaningful stratification of the photophobia prevalence by key demographic parameters (sex, age), traumatic brain injury severity, the mechanism of injury, presence of associated headache/migraine, and post-traumatic stress disorder. This stratification would be important because a more accurate characterization of photophobia natural history would likely bring about a deeper understanding of the specific differences in photophobia pathophysiology, including traumatic brain injury comorbid conditions such as migraine and post-traumatic stress disorder, which are known to affect photophobia symptoms.

Our analysis of prevalence at later periods since traumatic brain injury used data pertaining to the general population. It is possible that the availability of data from different subpopulations will allow for a refined assessment of the time course of photophobia for more specialized groups, which, in turn, will help develop optimal treatment and mitigation of this condition.

Lastly, photophobia does not have a dedicated International Classification of Diseases, Tenth Revision code, with the common and nonspecific use of H53.14 (“visual discomfort”) and/or H53.71 (“glare sensitivity”) in lieu of a code for photophobia, which likely contributed to a nonuniform reporting of this condition.

Recommendations

A comprehensive photophobia-dedicated validated questionnaire for patients with traumatic brain injury would greatly improve data analysis and the understanding of natural history of traumatic brain injury–associated photophobia and the relative effectiveness of management and rehabilitation of this condition. Development of a clinically practical automated quantitative instrumentation with high reproducibility will have a significant impact on the assessment of photophobia. Availability of a specific International Classification of Diseases, Tenth Revision coding for photophobia would greatly improve photophobia surveillance, and the availability of uniform and quantitative data would help to shed light on the physiological and cellular mechanism of photophobia and its association with many pathological conditions.

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