R E V I E W Open Access
Photophobia in neurologic disorders
Yiwen Wu and Mark Hallett
Photophobia is a common symptom seen in many neurologic disorders, however, its pathophysiology remains
unclear. Even the term is ambiguous. In this paper, we review the epidemiology and clinical manifestations of
photophobia in neurological disorders, including primary headache, blepharospasm, progressive supranuclear palsy,
and traumatic brain injury, discuss the definition, etiology and pathogenesis, and summarize practical methods of
diagnosis and treatment.
Keywords: Photophobia, Migraine, Blepharospasm, Progressive supranuclear palsy, Traumatic brain injury, Melanopsin
Photophobia refers to a sensory disturbance provoked by
light. The term photophobia, derived from 2 Greek words,
photo meaning “light”and phobia meaning “fear”, literally
means “fear of light”. Patients may develop photophobia
as a result of several different medical conditions, related
to primary eye conditions, central nervous system (CNS)
disorders and psychiatric disorders. Since the original lit-
erature described the manifestations of photophobia ,
many developments have taken place that makes it pos-
sible to establish a more precise picture of photophobia.
In this paper, we will review its presence in neurological
disorders, focusing on the definition, epidemiology, eti-
ology, clinical manifestations, pathogenesis, diagnosis and
In 1934, photophobia was first described and defined by
Lebensohn as “exposure of the eye to light definitely in-
duces or exacerbates pain”. This definition emphasized
that the core character is pain, but did not specify what
kind of light (e.g., bright light or dim light) caused the
symptom. In fact, photophobia is heterogeneous. Descrip-
tions of photophobia vary among patients, and some of
the heterogeneity comes from the different disorders that
manifest this symptom. For example, some patients with
migraine will deny that pain is a part of the experience at
all but just prefer to be in a darkened room . Thus,
some researchers believe that photophobia involves not
only the pain pathway, but also a limbic system pathway
that superimposes an emotional discomfort leading to
avoidance of light [3, 4]. Due to the evidence from basic
research and the limitations of the earlier definition, Fine
and Digre used the term “photo-oculodynia”to describe
the pain or discomfort in the eye arising from a light
source that should not be painful or discomforting under
ordinary circumstances . The term “photophobia”is
defined by Digre and Brennan as a sensory state in which
light causes discomfort in the eye or head; it may also
cause an avoidance reaction without overt pain .
Although there is no consensus definition of photophobia
in the field, this definition proposed by Digre and Brennan
seems more encompassing and descriptive.
The etiology of photophobia can be subdivided in four
main sections: (1) Orbital and visual pathway pathology
(e.g., ocular disorders, optic nerve and chiasm problems);
(2) Neurological disorders (e.g., primary headache, bleph-
arospasm, traumatic brain injury), (3) Psychiatric disorders
(e.g., agoraphobia, anxiety disorder, depression.); and (4)
Drug-induced photophobia (e.g., barbiturates, benzodiaze-
A number of neurologic conditions are associated
with photophobia (Table 1). The most common neuro-
logical conditions encountered are primary headaches,
benign essential blepharospasm (BEB), Progressive
supranuclear palsy (PSP) and traumatic brain injury
(TBI) . This review will focus on photophobia
present in these conditions.
* Correspondence: firstname.lastname@example.org
Human Motor Control Section, National Institute of Neurological Disorders
and Stroke, National Institutes of Health, 10 Center Drive MSC 1428, Building
10, Room 7D37, Bethesda, MD 20892, USA
© The Author(s). 2017 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0
International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and
reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to
the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver
(http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
Wu and Hallett Translational Neurodegeneration (2017) 6:26
Photophobia in neurologic disorders
Primary headaches include migraine, tension-type head-
ache (TTH), cluster headache and other trigeminal auto-
nomic cephalalgias, and other less frequent headache
types according to the International Classification of
Headache Disorders, 3rd edition (ICHD-III) . Photo-
phobia is a common and debilitating symptom often
present in migraine and other primary headaches. In a
population-based epidemiological study of primary head-
ache in Croatia in 2014 (n= 2350), up to 40% of patients
reported the symptom .
Photophobia is noted in 80%–90% of patients with mi-
graine, which is higher than that in other primary head-
aches [10, 11]. Patients with migraine experience the
symptom both during and between the attacks , but it
occurs more during the attack than after . Recent
research has shown a clear association between migraine-
related allodynia and photophobia only in chronic
migraineurs [14, 15]. These findings suggest that light
stimulation may contribute to central sensitization of
pain pathways in migraineurs, possibly contributing to
progression into chronic forms. Although the exact
prevalence of photophobia in TTH and cluster head-
ache patients is not precisely known, clinical studies
showed that subjects with TTH and with cluster head-
aches had more light sensitivity than controls [16, 17].
One study showed that patients with TTH had lower
discomfort thresholds to white light than controls, but
had higher thresholds than patients with migraine. It
may explain why photophobia is more common in pa-
tients with migraine than in patients with TTH ,
and indicates that light sensitivity may be present, but
not noticeable to every patient with TTH. Whether the
symptom can be unilateral or not still remains contro-
versial. Experimental evidence showed that photopho-
bia is bilateral even when the headache is unilateral in
primary headaches [13, 17]. On the other hand, unilat-
eral photophobia has been reported with cluster head-
ache, hemicrania continua, and other trigeminal
autonomic cephalagias [19, 20]. A prospective clinical
study of short-lasting unilateral neuralgiform headache at-
tacks with conjunctival injection and tearing or cranial
autonomic features showed that unilateral photophobia is
present in more than 40% of patients . More work is
necessary to describe the exact clinical features (bilateral
or unilateral) of photophobia by using a more detailed
Blepharospasm, often called benign essential blepharo-
spasm (BEB), is one of the most common focal dysto-
nias. It is characterized by involuntary orbicularis oculi
muscle spasms that are usually bilateral, synchronous,
and symmetrical . Photophobia is a prominent com-
plaint of patients with blepharospasm. One study dem-
onstrated that patients with blepharospasm were as light
sensitive as patients with migraine between the migraine
attacks, and that both groups were more light sensitive
than controls . In a survey of 316 blepharospasm pa-
tients, 94% reported light sensitivity; ambient lighting
could provoke spasms about half of the time, but bright
light provoked spasms almost all of the time . An-
other study comprising 240 BEB patients showed that
photophobia was present in 25% of patients prior to the
onset of the blepharospasm, and up to 74% patients re-
ported the photophobia at the time of the neurological
examination . Furthermore, photophobia is consid-
ered the second most common factor which can impact
BEB patients’quality of daily life. The mechanism of
photophobia is still elusive. A case-control study studied
the effect of photochromatic modulation with tinted
lenses on the sensory symptoms of photophobia in bleph-
arospasm patients . The results indicated that wave-
length of light exposure may influence the symptoms of
photophobia in addition to the actual light intensity. In
contrast, another study found that the relevant feature for
photophobia is the light intensity and not the wavelength
at least as altered by the FL-41 lens . Whether symp-
toms are better relieved by reducing light in a specific re-
gion of the spectrum or just reducing the net flux is still
Progressive supranuclear palsy
Progressive supranuclear palsy (PSP), previously referred
to as Steele Richardson Olszewski syndrome, is a Parkin-
sonian Syndrome. Characteristic features of PSP include
vertical supranuclear gaze palsy and postural instability
with falls. A clinical cohort study of 187 patients with PSP
showed that photophobia occurred in 43% of patients
. Another prospective study showed that photophobia
is significantly more frequent in clinically diagnosed PSP
than corticobasal degeneration (CBD) (100% vs 18%,
p= 0.0002) . These results suggest that the presence
Table 1 Neurological conditions associated with photophobia
Primary headaches (most common in Migraine)
Progressive supranuclear palsy
Traumatic brain injury
Lesions of the thalamus
Wu and Hallett Translational Neurodegeneration (2017) 6:26 Page 2 of 6
of photophobia could be used to help clinicians differenti-
ate the two diseases.
Traumatic brain injury
Traumatic brain injury (TBI) can manifest with visual
dysfunction including deficits in accommodation, ver-
gence movements, versions, and field of vision as well
increased photosensitivity [29, 30]. Photophobia is one
of the most common visual complaints . Studies of
TBI have frequently addressed the issue of photosensi-
tivity and its prevalence. One study showed a preva-
lence of 50% in patients compared with 10% health
controls . Photosensitivity does not only occur in
the acute phase of brain injury, but also in the chronic
phase. However, it is still unclear if photophobia is a
primary or secondary symptom of the brain injury. Fur-
thermore, studies revealed that over years, about half of
the patients reported reduced photosensitivity (i.e., 10%
in the 1st year plus 40% after the 1st year), while 42%
remained the same, 3% increased and 5% waxed and
waned . The decrease in photosensitivity may be a
result of neural repair, neural adaptation and/or com-
Mechanism of photophobia
Since light is the cardinal stimulus for photophobia, pho-
toreceptors must be involved. There are at least five differ-
ent types of photoreceptors in humans: three kinds of
cones, rods and ipRGCs. Rods and cones in the outer
retina are the predominant photoreceptor cells of the
mammalian retina. Their high temporal and spatial sensi-
tivity to light forms the basis of image-forming vision. The
intrinsically photosensitive retinal ganglion cells (ipRGC),
which contain the melanopsin photopigment (HUGO
gene symbol OPN4), have been identified in recent years
. The ipRGC cells are atypical retinal photoreceptors
separate from classical rod and cone photoreceptors. Sev-
eral studies demonstrated that ipRGC play an important
role in non-image-forming light effects . The ipRGC
cells send their axons to the suprachiasmatic nucleus and
the Edinger-Westphal nucleus. In the suprachiasmatic nu-
cleus, these cells entrain circadian rhythms . In the
Edinger-Westphal nucleus, they control the pupillary light
reflex [34, 36, 37]. Furthermore, evidence accumulating
from animal models shows that ipRGCs are involved in
photophobia of rod- and cone deficient mice. [38, 39]. In
humans, ipRGCs were implicated in photophobia since
migraine patients who became blind from a complete lack
of rod and cone function still experience photoallodynia
compared with patients with enucleated eyes . Mela-
nopsin, the ipRGC photopigment, has peak sensitivity at
480 nm. Using the photic blink reflex, one study tried to
objectively quantify the ocular sensitivity to red (640 nm)
and blue (485 nm) light in patients with light sensitivity
and normal subjects. The data demonstrated an increased
photic blink reflex to blue light as opposed to red light in
light-sensitive patients . These results suggest that the
melanopsin signaling system may control light aversion
and the ipRGC may be the most important photoreceptor
cell in the pathophysiological mechanism of photophobia.
Although the discovery of the ipRGC cells appear to
make an advancement in understanding the mechanism
of photophobia, how light functions as a pain stimulus
remains elusive. Increasing evidence demonstrates that
at least 3 pathways can transmit this signal to the brain.
The first pathway was described by Okamoto et al. .
They investigated the pattern of neuronal activation in
the caudal brainstem after bright light stimulation using
quantitative Fos-like immunoreactivity in anesthetized
rats. The results showed that light activated the trigeminal
brainstem neurons through photoreceptors in the retina
(whether rod, cone or ipRGC), which in turn evoked ocu-
lar vasodilation and activation of pain-sensing neurons on
blood vessels . The second pathway for photophobia is
a direct connection between the ipRGC cells and thalamic
nuclei, which are associated with somatic sensation and
pain . The discovery of this second pathway is particu-
larly significant as the thalamus is an important center for
sensory integration, and has important connections to
somatosensory centers of the cortex . A third pathway
is suggested that does not involve the optic nerve. The
ipRGCs and/or ipRGC-like melanopsin-containing neu-
rons in the iris can contribute to the trigeminal afferents
bypassing the optic nerve [44, 45].
Neuropeptides that enhance synaptic transmission may
play a role in photophobia at multiple levels of the visual
and trigeminal pathways. Two particular candidates are
the calcitonin gene-related peptide (CGRP) and pituitary
adenylate cyclase-activating polypeptide (PACAP), both of
which may play a role in migraine attacks in migraineurs
. These multifunctional peptides are widely distributed
in the nervous system and in addition to their vascular ac-
tions; they are both implicated in modulating nociception.
Pre-clinical studies have linked both neuropeptides to
photophobia. Animal models showed that mice with a
gain-of-function mutation of CGRP receptor, exhibit light
avoiding behavior when they receive injections of calcium
gene-related peptide . Mice lacking PACAP do not de-
velop nitroglycerin-induced light aversion.
Diagnosis and evaluation of photophobia
Generally, the diagnosis of photophobia is established in
the history, along with neurologic and neuro-ophthalmic
examination. However, answering the usual question,
“does light bother you,”with a “no”should not be taken
as indicative of the absence of photophobia . Further
questioning with the use of more detailed closed-ended
questions is needed to detect the symptom and to evaluate
Wu and Hallett Translational Neurodegeneration (2017) 6:26 Page 3 of 6
the severity. Assessment tools for photophobia have been
sparse. Bossini et al. developed and validated a photopho-
bia questionnaire, a self-assessment tool established in
Italian populations  (Table 2). It consists of 16 items
investigating psychopathological traits and behavioral sen-
sitivity to light. The questions try to identify specifically
both behaviors that actively avoid light, termed photopho-
bia (items 2, 6, 7, 9, 10, 12, 13, 14) and that actively search
light, described as photophilia (items 1, 3, 4, 5, 8, 11, 15,
16), which have been identified as relevant to the Mediter-
ranean population in clinical practice. For each item the
patient may respond in a dichotomous way (yes or no).
Affirmative answers are rated as 1 and negative ones as 0,
except for item 5 where the scores are reversed (yes = 0,
no = 1). Two scores are obtained by the simple sum of
each item divided by the number of items for each dimen-
sion (8 for photophobia and 8 for photophilia); therefore,
two scores ranging from 0 to 1 identify photophobic and
photophilic behavior, respectively). Recently, Choi et al.
validated a questionnaire in order to assess light aversion
behavior in a reproducible way (Table 3) . Their
questionnaire seems to be a useful method for detecting
photophobia in patients with migraine in Korea. Although
this questionnaire has not been validated in populations
outside Korea, it may be useful to clinical researchers who
are trying to better understand photophobia.
Since the mechanism of the photophobia is still not
clear, the pharmacotherapeutic treatment remains un-
known. There is only little evidence that shows that the
systemic medication can relieve the photophobia itself,
but treating the underlying conditions may improve the
associated photophobia, such as migraine preventive or
specific medication (e.g., beta-blockers, calcium channel
blockers, anti-convulsants, CGRP-P) for patients with
migraine associated photophobia [51, 52, 53].
Botulinum neurotoxin (BoNT) is the treatment of
choice for blepharospasm and it also has some efficacy
in migraine headache. However, there is limited informa-
tion for the effect of BoNT on photophobia. A cohort
study showed that injection of onabotulinumtoxinA is
helpful for photophobia associated with TBI .
However, the efficacy needs to be further explored in
well-designed studies involving a large population of
patients. More work is necessary to evaluate the efficacy
of the BoNT in the treatment of photophobia in other
conditions as well .
Different photoreceptors have different spectral sensitiv-
ity to light. Maximum light sensitivities of human rods
(R), S cones, M cones and L cones are 500 nm, 420 nm,
530 nm and 560 nm wavelength, respectively. The ipRGCs
exhibit their peak sensitivity at 480 nm. There is some
evidence that patients with blepharospasm reported the
Table 2 Photosensitivity Assessment Questionnaire (PAQ)
Photosensitivity Assessment Questionnaire (PAQ)
1. I prefer summer to winter because winter dreariness makes me
2. If I could, I would be happier to go out after dusk rather than during
the day. (Pho)
3. Often in winter, I’d like to go to the other hemisphere where it is
summer time. (Phi)
4. My ideal house has large windows. (Phi)
5. I like cloudy days. (Phi)
6. Sunlight is so annoying to me, that I have to wear sunglasses when I
go out. (Pho)
7. I prefer to stay at home on sunny days, even if it is not warm. (Pho)
8. I feel reborn in spring when the days start to become longer. (Phi)
9. Usually strong sunlight annoys me. (Pho)
10. I prefer rooms that are in semi-darkness. (Pho)
11. I prefer sunlight to semi-darkness. (Phi)
12. Looking at a very bright view annoys me. (Pho)
13. I can’t stand light reflecting off snow. (Pho)
14. I think summer annoys me because it’s too bright. (Pho)
15. Sunlight is like therapy for me. (Phi)
16. I prefer walking in the sunlight if the weather is cool. (Phi)
Phi: photophilia; Pho: photophobia
These questions try to identify specifically both behaviors that actively avoid
light, termed photophobia (items 2, 6, 7, 9, 10, 12, 13, 14) and that actively
search light, described as photophilia (items 1, 3, 4, 5, 8, 11, 15, 16), which
have been identified as relevant to the Mediterranean population in clinical
practice. For each item, the patient may respond in a dichotomous way (yes or
no). Affirmative answers are rated as 1 and negative ones as 0, except for item
5 where the scores are reversed (yes = 0, no = 1). Two scores are obtained by
the simple sum of each item divided by the number of items for each
dimension (8 for photophobia and 8 for photophilia); therefore, two scores
ranging from 0 to 1 identify photophobic and photophilic
Table 3 Photophobia questionnaire for patients with primary
headaches (English version of the questionnaire developed by
Choi et al. )
1 During your headache, do you feel a greater sense of
glare or dazzle in your eyes than usual by bright lights?
2 During your headache, do flickering lights, glare, specific
colors or high contrast striped patterns bother you or
3 During your headache, do you turn off the lights or draw
a curtain to avoid bright conditions?
4 During your headache, do you have to wear sunglasses
even in normal daylight?
5 During your headache, do bright lights hurt your eyes? Yes No
6 Is your headache worsened by bright lights? Yes No
7 Is your headache triggered by bright lights? Yes No
8 Do you have any of the above symptoms mentioned
even during your headache-free interval?
The score ranges from 0 (no photophobia) to 8 (severe photophobia)
Wu and Hallett Translational Neurodegeneration (2017) 6:26 Page 4 of 6
best relief of photophobia with the FL-41 lens, which
blocks wavelengths around 480 nm . The use of dark
sunglasses indoors must be strongly discouraged. By wear-
ing dark glasses indoors, patients are dark adapting their
photorecetors and aggravating their sensitivity to light.
These patients should be encouraged to transition to the
use of FL-41 or other tints for indoor light sensitivity .
Photophobia is a common symptom seen in many
neurologic disorders. While the underlying mechanism
of photophobia is still elusive, the discovery of ipRGCs
appears to be an advance in understanding. The cal-
cium gene-related peptide receptors (for CGRP and
PACAP)) may be potential targets in the treatment of
headache and photophobia as well. Generally, the diag-
nosis of photophobia is established upon the history,
along with neurologic and neuro-ophthalmic examination.
Since a number of common ophthalmic conditions are as-
sociated with photophobia, patients should be referred to
an ophthalmologist to rule-out or treat these conditions if
the neurologic history and examination fail to suggest a
diagnosis. Furthermore, physicians should be encouraged
to use an assessment tool of photophobia or photophilia
for detecting the symptoms. Wearing specially tinted
spectacles may provide an effective means to relieve the
BEB: Benign essential blepharospasm; BoNT: Botulinum neurotoxin;
CBD: Corticobasal degeneration; CGRP: Calcitonin gene-related peptide;
CNS: Central nervous system; ipRGC: Intrinsically photosensitive retinal
ganglion cells; PACAP: Pituitary adenylate cyclase-activating polypeptide;
PSP: Progressive supranuclear palsy; TBI: Traumatic brain injury; TTH: Tension-
Thanks for the assistance of Lu He during the writing of the manuscript. Dr.
Hallett is supported by the NINDS Intramural Program.
Availability of data and materials
The work was supported by the National Natural Science Foundation of
China (No.81200981, 81,371,407), the Innovation Program of Shanghai
Municipal Education Commission (No.13YZ026), and the Intramural Program
of the National Institute of Neurological Disorders and Stroke.
YW wrote the first draft of the manuscript, MH revised and wrote the final
edition. Both authors read and approved the final manuscript.
Ethics approval and consent to participate
Consent for publication
The authors declare that they have no competing interests.
Received: 6 May 2017 Accepted: 29 August 2017
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