Differential diagnosis and theories of pathophysiology of post-traumatic photophobia: A review

Abstract

BACKGROUND:

Photophobia is a common sensory symptom after traumatic brain injury (TBI) that may have a grave impact on a patient’s functional independence, neurorehabilitation, and activities of daily living. Post-TBI photophobia can be difficult to treat and the majority of patients can suffer chronically up to and beyond one year after their injury.

OBJECTIVES:

This review evaluates the current theories of the pathophysiology of photophobia and the most-common co-morbid etiologies of light sensitivity in TBI to help guide the differential diagnosis and individualized management of post-TBI photophobia.

METHODS:

Primary articles were found via PubMed and Google Scholar search of key terms including “photophobia” “light sensitivity” “photosensitivity” “photo-oculodynia” “intrinsically photosensitive retinal ganglion cells” “ipRGC” and “concussion” “brain injury” “dry eye”. Due to paucity of literature papers were reviewed from 1900 to present in English.

RESULTS:

Recent advances in understanding the pathophysiology of photophobia in dry eye and migraine and their connection to intrinsically photosensitive retinal ganglion cells (ipRGC) have revealed complex and multifaceted trigeminovascular and trigeminoautonomic pathways underlying photophobia. Patients who suffer a TBI often have co-morbidities like dry eye and migraine that may influence the patient’s photophobia.

CONCLUSION:

Post-traumatic photophobia is a complex multi-disciplinary complaint that can severely impact a patient’s quality of life. Exploration of underlying etiology may allow for improved treatment and symptomatic relief for these patients beyond tinted lenses alone.

Keywords

Photophobia photosensitivity light sensitivity traumatic brain injury TBI ipRGC concussion

1 Introduction

Photophobia is often interchangeably referenced to as photosensitivity, light sensitivity, and/or light intolerance. These are general terms used to describe vast and variable subjective patient presentations where light causes discomfort or pain in the eye and/or head. The Greek translation for photophobia is “fear of light” which can be an accurate description of patients who develop a behavioral aversion to light. However, not all patients with behavioral avoidance of or aversion to light may experience overt pain, and not all patients who experience pain with light exposure may adopt behavioral avoidance or aversion.

The differentiation of types of photophobia was initially characterized in the literature in 1934, when Lebensohn elaborated on the difference between “true photophobia” where light exposure induces or exacerbates eye and head pain, versus “dazzle-induced” photophobia, in which case the patient has visual discomfort due to poor diffusion of light through the ocular media as can occur with corneal, lenticular, and vitreous opacities (Lebensohn, 1934). Most recently, newer terminology, “photo-oculodynia” and “photoallodynia” has emerged, which is used to describe patients who have pain induced by a light source that should not be painful under normal circumstances, like ambient room lighting (Digre & Brennan, 2012). In this review, photophobia will elude to the “true photophobia” described by Lebensohn where light exposure exacerbates eye or head pain, glare sensitivity will be used to describe the aforementioned “dazzle photophobia,” and photo-oculodynia will be used as it is currently defined and be used in place of photoallodynia. This differentiation is important as patients post-TBI may experience one or all of the aforementioned types of light sensitivity.

Light and glare sensitivity are common sensory symptoms in traumatic brain injury (TBI) and numerous other neurologic conditions. The identification and management of light sensitivity is crucial to best-practice neurorehabilitation and directly impacts a patient’s functional independence (Lew et al., 2009). True photophobia can influence a patient’s ability and desire to return to brightly lit settings like schools, medical offices, workplaces, grocery stores, restaurants, gyms, and the outdoors. Thus, photophobia can significantly impact a patient’s quality of life due to the resultant increased social isolation which can reduce physical functioning, general health, social functioning, and further impact the patient’s emotional and mental health (Callahan & Lim, 2018; Shepherd et al., 2020).

Presently, there is a lack of clinically available objective diagnostic tools to diagnose and quantify light sensitivity post-TBI. While patients may present with objective behavioral aversions to light including squinting, tearing (Lebensohn, 1951), excessive blinking (Wu et al., 2019), and eye movements causing fixation loss (Lin et al., 2015), even well-trained clinicians are unable to accurately diagnose TBI-related photophobia versus controls based upon these observations alone (Yuhas et al., 2019). Thus, the diagnosis of post-TBI photophobia is currently limited to non-standardized clinical assessment of subjective patient symptomatology including patient history of or denial of pre-injury light sensitivity compared to post-injury light sensitivity, and timeline of light sensitivity onset with history of brain injury.

To further complicate the accurate diagnosis and treatment of post-traumatic photophobia, light sensitivity has a multitude of differential diagnoses, including ocular, neurological, psychological, and pharmacologic etiologies (Digre & Brennan, 2012; Katz & Digre 2016). When a patient suffers from a TBI, they may have pre-existing and/or develop a number of comorbid conditions that in isolation of TBI can present with photophobia. These conditions include but are not limited to dry eye, ocular inflammation, corneal disorders (Lebensohn et al., 1951), intermittent exotropia (Oh et al., 2014), subarachnoid hemorrhage (Aydin et al., 2016; Cavus et al., 2014), depression (Anagnostou et al., 2017; Seidel et al., 2017), secondary blepharospasm (Anagnostou et al., 2017), anxiety, stress (Seidel et al., 2017), ADHD (Kooij & Bijlenga, 2014), increased intracranial pressure/papilledema (Sabo et al., 2018), migraine, cluster headache, cervicogenic headache, and tension-type headache (Anagnostou et al., 2017; Vanagaite Vingen & Stovner, 1998), as well as post-traumatic use of pharmaceuticals with pupillary dilation side effects like anticholinergics, serotonin reuptake inhibitors, and adrenergics (Pula et al., 2013). The treatment of photophobia post-TBI depends upon the underlying etiology of the photophobia. This review evaluates the current theories of the pathophysiology of photophobia and the most-common co-morbid etiologies of light sensitivity to help guide the differential diagnosis and individualized management of post-TBI photophobia.

2 Epidemiology

Frequently included as part of comprehensive post-TBI symptom scales, rates of photophobia in the TBI population can vary depending upon the format of the questionnaire from 11.3% in an open-ended questionnaire to 52.1% in a closed-ended questionnaire (Emmert et al., 2021). The subjective quality of photophobia is inconsistently assessed post-TBI, and while questionnaires like the Visual Light Sensitivity Questionnaire-8 (VLSQ-8) and the Utah Photophobia Symptom Impact Scale (UPSIS-12) has been validated in the general population (Verriotto et al., 2017; Cortez et al., 2019), there is yet to be a standardized nor validated photophobia questionnaire that assesses photophobia presence and severity that is validated in the TBI population (Callahan & Lim, 2018). While it is more common for patients to report photophobia post-TBI compared to healthy controls (Capo-Aponte et al., 2012; Lew et al., 2009), reported epidemiology of post-TBI photophobia is inconsistent and limited due to the subjectivity of clinical photosensitivity reporting, variability of clinical assessment tools, as well as non-standardized terminology (Callahan & Lim, 2018).

3 Pathophysiology of photophobia

The pathophysiology of photophobia is inherently complicated as it is dependent upon the neural pathways that control how much light enters the eye, how the eye responds to different wavelengths of light, and how the eye is connected to the trigeminovascular pain system. When light enters the eye, it is focused by the cornea and the lens onto the back of the eye, known as the retina, which contains photoreceptors called rods and cones. Rods contain the photopigment rhodopsin, and the three types of cones (L-,M-,S-) which contain erythrolabe, chlorolabe, and cyanolabe photopigments respectively. When stimulated by light, these photoreceptors synapse with retinal ganglion cells (RGC), whose axons leave the eye as a bundle, called the optic nerve, to translate the light information to the visual cortex via the afferent visual pathway which contains the anatomical landmarks known as the lateral geniculate nucleus and superior colliculus. This is known as the retino-geniculo-cortical or image-forming afferent visual pathway and is responsible for “what” we see. In addition to visual image formation, light is also important for non-image forming biological functions including but not limited to photic regulation of the circadian rhythm (Bonmati-Carrion et al., 2016; Hattar et al., 2002), pupillary light reflex (Bonmati-Carrion et al., 2016; Lucas et al. 2001), hormonal secretion (Lucas et al., 1999), body temperature, alertness, sleep (Badia et al., 1991; Rupp et al., 2019), and mood (Fernandez et al., 2018), which follows a different visual neuronal projection in the brain.

Of the estimated 1.0–1.2 million RGCs in the human retina (Curcio & Allen, 1990), it has been recently discovered that 0.63–0.75% of human RGC ∼ 7,500 (Hannibal et al., 2017) contain a separate photopigment called melanopsin, making them intrinsically photosensitive retinal ganglion cells (ipRGCs) (Provencio et al., 2000). The ipRGCs melanopsin photopigment has a peak light absorption sensitivity to 479nm of light (Lucas et al., 2001), and can be directly stimulated by light as well as indirectly through input signals from surrounding rods and cones (Wong et al., 2007). ipRGC axons project out of the eye through the optic nerve along the afferent visual pathway through the optic chiasm. However, unlike the majority of image-forming RGCs that project axons along the retino-geniculo-cortical pathway, the majority of axons of ipRGCs decussate from the optic tract after the optic chiasm and send axons to other brain nuclei. ipRGC retinorecipient brain nuclei include the suprachiasmatic nucleus in the hypothalamus, the intergeniculate leaflet in the thalamus and the olivary pretectal nuclei in the midbrain (Beier et al., 2021). Thus, ipRGCs are implicated in the aforementioned non-image forming biological functions including photoregulation of the circadian rhythm, the pupillary light reflex (Lucas et al., 2001), the light-pain matrix (Noseda et al., 2010; Okamato et al., 2009), and light aversion (Matynia et al., 2012).

4 How light enters the eye – The pupillary light reflex

The amount of light that shines on the retina is controlled by the size of the pupil, which is regulated by the pupillary light reflex (PLR). It is evolutionarily important to control the amount of light entering the eye to prevent overexposure light damage to the retina and allow for appropriate depth of focus and visual clarity in various lighting settings. As the pupil size increases, the depth of focus decreases, and optical aberrations increase, thus visual acuity can decrease with increasing pupil size (Campbell & Gregory, 1960). The PLR is an autonomically innervated visual reflex that reflects a balance between the parasympathetic innervation of the iris sphincter muscle, which causes pupillary constriction (miosis) and the sympathetic innervation of the iris dilator muscle, which causes pupillary dilation (mydriasis) (Heller et al., 1990). The PLR is driven directly by light signals transduced by ipRGCs through the pretectal olivary nuclei (Hattar et al., 2003, Okamato et al., 2010).

The size of the pupil is dictated primarily by the amount and intensity of light shining on the eye and is constantly in flux depending upon the ambient room lighting and balance of parasympathetic and sympathetic tone (McDougal & Gamlin, 2015). Pupil size can also be influenced by a number of external factors including but not limited to visual accommodation on near targets (Kasthurirangan & Glasser, 2005), the complexity of visual targets viewed (Gamlin et al., 1998), vascular disease, trauma, ocular disease (Payne et al., 2021) cognitive attention, emotion, pharmacological agents, and neurologic disease (McDougal & Gamlin, 2015; Wilhelm, 2011).

Abnormal mydriasis may occur due to disease, trauma to the parasympathetic PLR pathway, and pharmacological inhibition of the parasympathetic PLR pathway by anticholinergic drugs or excitation of the sympathetic PLR pathway by adrenergic or dopaminergic drugs (McDougal & Gamlin, 2015). Atypical mydriasis can let more light onto the retina and cause light sensitivity (Aydin et al., 2016) as well as blurred near vision due to reduced accommodation and increased optical aberration (Campbell & Gregory 1960).

5 What makes light painful? The light-pain matrix

At this time, there are multiple trigeminovascular and trigeminoautonomic pathways that are implicated in the pathophysiology of photophobia. The discovery of melanopsin and ipRGCs in 1999 (Provencio et al., 2000) has led to a rapid increase in research into this area, and further knowledge of photophobia pathophysiology is likely to emerge in the future. The following paragraphs summarize current literature hypotheses regarding neural pathways, which are still being actively researched at the time of publication of this review.

5.1 Photophobia due to direct activation of the ophthalmic trigeminal afferent pathway

Afferent sensory branches of the ophthalmic division (V1) of the trigeminal nerve innervate the anterior parts of the eye including the conjunctiva, cornea, sclera, ciliary body, choroid, trabecular meshwork, and iris, while trigeminal efferent branches can be found in blood vessels of the eye and orbit (McDougal & Gamlin, 2015). When these structures are damaged or inflamed, the afferent trigeminal nociceptive pathway is activated and the V1 trigeminal afferents project to the trigeminal ganglion, and ultimately terminate in the spinal trigeminal nucleus (Panneton et al., 2010). From the trigeminal nucleus, second order neuronal axons can project to the thalamus for further relay to the somatosensory cortices for pain (Noseda et al., 2010), and the superior salivatory nucleus which can activate parasympathetic effectors that ultimately lead to reflex lacrimation (Okamoto et al., 2012) and conjunctival injection and periorbital eye pain due to vasodilation of ocular blood vessels (Okamato et al., 2012).

Photophobia that occurs during corneal damage can directly activate this trigeminal afferent pathway (Okamato et al., 2010) and ipRGCs in the retina and iris can directly activate the afferent trigeminal nociceptors in the eye and orbit (Dolgonos et al., 2011).

5.2 Photophobia due to retino-pretectal parasympathetic- and retino-hypothalamic- sympathetic-trigeminovascular pathway

ipRGC parasympathetic projections to the olivary pretectal nucleus and sympathetic projections to the hypothalamus can both lead to neuronal stimulation of the superior salivatory nucleus (Baver et al., 2008 Elenberger et al., 2020; Katagiri et al., 2013; Okamato et al., 2010). Thus, in the absence of mechanical damage to the eye, light can indirectly activate the aforementioned trigominovascular reflex leading to parasympathetic vasodilation of ocular blood vessels and light-exacerbated eye pain. This is the proposed pathway for photo-oculodynia (Noseda & Burstein 2011; Okamato et al., 2010) and may be one of the pathways involved in the photophobia that can occur due to direct orbital and ocular trauma like corneal abrasions, iritis, uveitis, and dry eye, among many other ocular conditions that can present with photophobia (Digre & Brennan 2012; Katz &Digre 2016, Elenberger et al., 2020)

5.3 Photophobia due to the retino-thalamo-cortical pathway

Alternatively, axons from some of the retinal ipRGCs have been found to project directly to the posterior thalamus, which then projects axons to the somatosensory, visual, and associative cortices for pain perception. Studies by Noseda (2010) have shown that signals from retinal ipRGCs converge with dura-sensitive trigeminovascular neuronal signals from the meninges in the posterior thalamus, and the retino-thalamo-cortical pathway has been implicated in the pathophysiology of light-induced exacerbation of pain in headache and migraine (Noseda et al., 2010).

At this time, the exact pathophysiology of post-TBI photophobia is unknown. While there are multiple independent neurological pathways responsible for the light-pain matrix (Dolganos 2011; Noseda et al., 2010; Okamato et al., 2009), the correlation of photophobia co-morbid diagnoses like migraine, dry eye, TBI and sleep disorders has led some to postulate that there may be an underlying commonality in pathophysiology (Diel et al., 2021; Elenberger et al., 2020).

6 Differential diagnosis of post-tbi photophobia

Most patients with post-traumatic photophobia may notice pain provocation with specific types of lighting like fluorescent (26%) or outdoor lighting (10%), more so than indoor lighting (6%), while some patients may report sensitivity to all types of lighting (21%). These statistics need further validation, as studies differentiating light sources are limited in number (Truong et al., 2014), and clinicians and most symptom questionnaires regarding post-TBI photophobia may ask patients only about the presence and severity of photophobia but not the specific light source (Callahan & Lim, 2018).

Photophobia can occur in all stages of TBI, including acute, subacute, and chronic (Capo-Aponte et al., 2012; Truong et al., 2014). The majority of patients post-TBI suffer chronically from light sensitivity, with only 10% of TBI patients noting reduction in light sensitivity within the first-year post-injury, 29–40% noticing reduction in light sensitivity after the first year, and up to 42% of patients noting stability in their light sensitivity complaints one year after their injury (Truong et al., 2014; Shepherd et al. 2020).

The ambiguity in pathophysiology has led to difficulty in treating photophobia in this population and persistence of post-TBI photophobia. Co-morbid risk factors associated with inhibiting post-TBI photophobia improvement include hyperacusis, loss of consciousness at the time of injury, dry eye, migraine, and use of tinted lenses (Troung et al., 2014). Clinically, photophobia symptoms can vary in regards to time of onset, duration, variability, light source, and concomitant ocular symptoms depending upon the etiology. A detailed case-history may reveal the photophobia in a patient post-TBI is actually due to a co-morbid condition and may respond to a more directed treatment.

6.1 Photophobia and abnormal pupillary mydriasis

As aforementioned, patients with abnormally large pupils can complain of photophobia, glare sensitivity, and reduced visual acuity (Ueda et al., 2007). It should be noted that not all patients with large pupils have photophobia complaints, and “normal” pupil size varies greatly between individuals due to the numerous external factors impacting pupil size as well as the variability in current diagnostic pupillometers (Mantry et al., 2005). Thus, abnormal pupillary mydriasis as mentioned here refers to abnormal size and function for the individual. Post-TBI unilateral mydriasis may occur if there was direct damage to the iris sphincter muscle or along the parasympathetic PLR pathway. Additionally, pharmacologic mydriasis can occur post-TBI as many medications that are commonly employed for co-morbid post-traumatic conditions have mydriatic side-effects. Pharmacologic unilateral mydriasis usually occurs due to inadvertent eye contact with a topical medication prior to washing one’s hands. This can occur in post-TBI patients who touch their eye after placing a scopolamine patch behind their ear in attempts to ameliorate motion sickness or nausea (Lee et al., 2013). Bilateral mydriasis may occur with systemic medications that include but are not limited to adrenergic stimulants like amphetamines that are used to treat ADHD, selective serotonin reuptake inhibitors to treat depression and anxiety (Pula et al., 2013), seizure medications like dilantin (Ioannidis, et al., 2016) and any other drug that causes anticholinergic toxicity may cause mydriasis and subsequent onset of light sensitivity. In these cases, an accurate case history of topical and oral prescription and herbal medications used, dosage, timing and topical location of drug administration relative to onset of photophobia may be key to diagnosis of pharmacologic mydriasis, which in most cases will self-resolve after discontinuation of the medication.

6.2 Photophobia and direct orbital trauma

If a patient with post-TBI photophobia has a history of direct trauma to the eye, they should be referred to an optometrist or ophthalmologist for urgent evaluation and management of possible ocular complications if they have not already been seen. Direct orbital trauma can cause an extensive number of ocular injuries, specifics of which are beyond the scope of this paper. In particular, corneal abrasion, inflammation of the iris (iritis) and ciliary body (uveitis), and iris sphincter muscle damage, can all cause photophobia independent of TBI through direct stimulation of the trigeminal afferent pathway (Digre & Brennan, 2012) and can be easily undiagnosed without ophthalmologic slit lamp examination. The more superficial the corneal lesion, the more severe the photophobia (Lebensohn 1934). In addition to photophobia that usually begins around the time of orbital trauma, patients with corneal abrasions will have intense eye pain that worsens with blinking, as well as tearing, and in some cases reduced vision. In the case of traumatic iritis or uveitis, the patient may not complain of photophobia until a few hours or even days after direct ocular injury and will usually also complain of a dull ache or throbbing pain in or around the eye, tearing and circumlimbal conjunctival injection (redness around the iris) (Bagheri et al., 2016). While patients with corneal abrasion, iritis, and uveitis have pain due to direct damage/signaling to the afferent nociceptors in the anterior segment of the eye, there are no studies indicating that these patients are sensitive to specific wavelengths of light. These patients may experience glare sensitivity due to improper diffusion of light through the cornea and anterior vitreous, which would make their sensitivity dependent on luminous intensity (brightness) of the light stimulus (Lebensohn 1934). Photophobia in these cases will be ameliorated by treatment of the underlying ocular condition and is limited to the duration of the inflammatory borne photophobia.

6.3 Photophobia and dry eye

Dry eye is present in 5–50% of the general population globally, depending on the population studied (Stapleton et al., 2017). There are numerous genetic, environmental, and pharmaceutical risk factors for dry eye including increased age, female gender, computer use, and contact lens wear (Craig et al., 2017) as well as different types of dry eye differentiated by clinical presentation like tear film insufficiency, meibomian gland dysfunction, and corneal findings such as keratoconjunctivitis sicca. Recent studies have shown that dry eye is also more common in patients with migraine (Ismail et al., 2019), sleep deprivation (Li et al., 2018), and post-TBI (Lee et al., 2018) than the general population. Patients with TBI have a higher incidence of sleep disorders than the general population (Leng et al., 2021). Dry eye symptoms including photophobia from sleep deprivation can occur within two days of sleep deprivation due to compromised lacrimal gland function (Lee et al., 2014;Li et al., 2018).

Patients who complain of light sensitivity from dry eye usually note variability in symptoms, with light sensitivity being worse in the beginning or end of the day along with the severity of their dry eye. Depending on the amount and chronicity of ocular surface damage from dry eye, patient’s light sensitivity complaints can vary and include glare sensitivity, photophobia, and photo-oculodynia and are usually accompanied by other ocular symptoms including tearing, itching, and redness (Galor et al., 2018). Patients with symptomatology suspicious for dry eye may find relief from dry eye treatment including but not limited to artificial tears, warm compresses, and eyelid hygiene routines. Dry eye is a complicated ocular surface disorder, that can be multifactorial in etiology and type, and take weeks to months to notice symptom improvement. Further studies are needed to differentiate if a specific type of dry eye is more common in patients with co-morbidities like migraine and TBI, as treatment varies depending upon the ocular health findings. Treatment of dry eye is best directed by eyecare providers. Some patient may have symptoms of dry eye but lack objective ocular signs on ophthalmologic examination and/or not find improvement in symptoms with standard ophthalmologic treatment of dry eye. In these cases of photophobia/photo-oculodynia, some have proposed the alternative and/or concomitant diagnosis of neuropathic ocular pain (Galor et al., 2018).

6.4 Photophobia and migraine

Photophobia can present in numerous primary headache disorders including migraine, tension-type, cervicogenic, and cluster headaches (Anagnostou et al., 2017; Vanagaite Vingen & Stovner, 1998). Up to 80% of patients with migraine complain of severe light sensitivity both during and between their migraine attacks (Diel et al., 2018). For some patients light can exacerbate and/or trigger migraine (Noseda et al., 2010). Unlike dry eye related light sensitivity, migraine photophobia is wavelength dependent, with short and long wavelengths in the visible spectrum being the most uncomfortable (Noseda et al., 2016). Interestingly, 480nm (blue) light has been found to be particularly triggering in patients with migraine, which also happens to be in the action spectrum of ipRGCs (Lucas et al., 2001) as well as commonly emitted by fluorescent lights and electronic devices. Patients with migraine headaches have a documented history of intolerance to fluorescent lighting (Wilkins et al., 1991). Due to the wavelength variability of headache exacerbation with light, many patients have noted subjective improvement with precision ophthalmic tints which can selectively filter various wavelengths and have been shown to decrease light-induced cortical hyperactivity (Huang et al., 2011). In particular, FL-41 tinted lenses, which have minimal transmission at 480nm, the same action spectrum as ipRGCs, have been found to provide relief in patients with migraine and blepharospasm (Blackburn et al., 2009; Katz & Digre 2016).

7 Treatment of post-traumatic photophobia – Tinted lenses and beyond

Given the numerous neural pathways from which light can cause pain, it is not surprising that photophobia complaints by patients are variable. Even though the symptomatology of photophobia can be vastly different between patients, the most commonly prescribed treatment from providers is for acute symptomatic relief with recommendations to avoid lights, electronic devices, and use sunglasses. Tinted lenses have been documented to be helpful in reducing headache exacerbation in migraine patients (Huang et al., 2011), and subjectively mitigate post-TBI photophobia symptoms for some but not all patients while they are wearing the lenses (Clark et al., 2017; Fimreite et al., 2016). However, retrospective analysis in chronic post-traumatic photophobia has shown that patients who did not wear tinted lenses were more likely (71%) to exhibit reduction in photophobia symptoms compared to patients who did wear tinted lenses (36%). Hypotheses for this finding includes patients voluntarily tapering the wear of tinted lenses organically over time as their photophobia improved, and/or the tinted lenses themselves interfering with neural adaptation (Troung et al., 2014).

A concern with long-term use of tints in the TBI population, as well as constant use of sunglasses indoors, is that these behaviors may interfere with or inhibit the natural neural adaptation to light and/or exacerbate photophobia due to retinal dark adaptation (Digre & Brennan, 2012; Katz & Digre 2016). Dark adaptation is an innate property of the retina, where the rods and cones recover their light sensitivity threshold (ie regenerate their photoreceptor photopigments) after exposure to light. When the retina is deprived of light as can occur in dimly lit settings like homes where patients keep their lights off and/or wear sunglasses indoors constantly, the retina can become hypersensitive to light, which is subjectively noticeable upon reintroduction of a light stimulus. Therefore, while sunglasses are recommended for outdoor use to all patients to preserve ocular health from UV light damage, the use of sunglasses indoors is strongly discouraged as it may aggravate light sensitivity over time (Katz &Digre 2016; Lebensohn 1934; Truong et al., 2014).

Some patients with extreme post-TBI photophobia may necessitate and benefit from acute management of their symptoms with tinted lenses (Clark et el., 2017) and some patients who wear tinted lenses post-TBI will still notice reduction in photophobia symptoms over time (Truong et al., 2014). Thus, the clinical balance of acute symptom management but need for long term resolution of photophobia is a current dilemma in treating this patient population as the tinted lenses may slow down the neural adaptive process but be necessary for patient comfort. For extreme cases where indoor sunglass use is mandated by the patient, the provider may want to consider reducing or titrating tint density over time or transitioning the patient to wavelength-specific photochromic tints, like FL-41. There is an inherent need for further research into the timing of prescription of tinted lenses, wavelength and density of tinted lenses used, and titration of tint density over time in the post-TBI population in regards to appropriate tint management of post-TBI photophobia. For patients where tinted lenses have not provided relief, further management options should be considered to treat co-morbid etiologies including those aforementioned as well as contact lenses (Truong et al., 2014), trigger point injections (Freeman et al., 2009) superior cervical sympathetic blockade (Fine & Digre, 1995), and botox (Bellieveau & Jordan 2012; Diel et al., 2018).

The best way to treat photophobia is to treat the underlying disorder, which requires a detailed case history regarding the patient’s subjective experience in relation to light exposure. Unfortunately, there is an absence of standardized and validated diagnostic tools for photophobia including photophobia symptom surveys for the TBI population. As made evident by Emmert et al. (2021), the questions we ask our patients and how we ask them is important and can elicit different results and further studies into photophobia questionnaires is warranted.

It is the authors opinion based on the evidence presented, that patient history details collected to aid in the differential diagnosis of photophobia should include but not be limited to:

Time of onset of photophobia symptoms after the TBI – did it occur directly after the trauma or after they started a medication?

Documentation of pre-existing photophobia symptoms or risk factors that can cause photophobia independent of TBI

Type and location of physical symptoms of pain triggered by light – is the pain in the eye or the head and/or does it radiate towards/from the neck?

Variability of the photophobia with time – is it constant since the TBI or does it fluctuate with headache, ocular dryness, or time of day?

Relation of photophobia to headache and/or migraine symptoms

Types of lighting that trigger symptoms – is the patient only triggered by short-wavelength light sources like fluorescent lights, computers, and sunlight, or are they triggered by any visible light wavelength? Are they triggered by static lights or flickering lights?

What factors exacerbate and/or ameliorate the pain?

What lifestyle behaviors have they adopted to compensate?

In general, the current literature lacks prospective clinical trials, is limited by small sample sizes, and lacks agreement in treatment modalities. Since photophobia can be from multiple factors, it may require multidisciplinary management and require referrals to providers outside of eyecare, including physiatrists, physical therapists, psychiatrists, and neurologists.

8 Conclusion

The normal physiological response to light should be painless. Post-TBI patients may have glare sensitivity, photo-oculodynia, true photophobia, and/or a combination of all three. True photophobia post-TBI is pathological and may have a multifactorial etiology due to the numerous co-morbid conditions that can occur post-TBI including migraine, cervicogenic headache, dry eye, and psychiatric conditions as well as side effects from medications and retinal dark adaptation from overuse of tinted lenses. It has been hypothesized in the literature that some of these co-morbidities share an underlying pathophysiology that may be driven by the multifaceted ipRGC non-image forming visual pathways. As the pathophysiology of the light-pain matrix and the role of ipRGCs becomes better understood, more targeted treatment options for post-traumatic photophobia may emerge. Since photophobia has a drastic impact on the patient’s quality of life and rehabilitation, it is imperative that the clinician understand the pattern recognition of different types of photophobia depending upon the underlying pathophysiological cause, to help guide the treatment and ultimately lead to not just symptomatic relief of photophobia but long term remediation altogether.

Conflict of interest

The author has no conflicts of interest related to the contents of this review.

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