New Objective Methods for

Understanding the Cause and 

Treatment of Photosensitivity

Randy Kardon MD PhD

Professor and Director of Neuro-ophthalmology,, Dept. of Ophthalmology and Visual Science, 

University of Iowa Hospital and Veterans Administration, Iowa City, Iowa

Director of Iowa City VA Center of Excellence for the Prevention and Treatment of Visual Loss

Funded by the Department of Veterans Affairs, and DOD (TATRC)
I have the following financial interests or relationships 

to disclose:

 Funding from NEI R009040554; R01 EY018853 

 Funding from Department of Defense; TATRC

 Funding from VA Rehabilitation Research and Development

 Novartis steering committee OCTiMS

 Acorda steering committee visual symptoms

 Zeiss Meditec consultant for perimetry and OCT

FINANCIAL DISCLOSURE
Poll Question 1

Which is your main role at the VA?

•1) Ophthalmologist

•2) Optometrist

•3) Neurologist

•4) Primary Care Physician or Physician’s Assistant

•5) Occupational/Physical Therapist

•6) Social Worker

•7) Research Scientist
Poll Question 2

How many new patients with photosensitivity 

do you see per year?

• 1) 1-5 patients

• 2) 6-10 patients

• 3) 11-20 patients

• 4) >20 patients
Photosensitivity

 Associated with acute uveitis

 Common in retinal dystrophies

 Can occur following meningitis

 A major symptom in some brain 

tumors

 More common in patients with 

migraine

 Common after TBI (59% report it)

 Psychogenic component? 
Noseda R, Kainz V, Jakubowski M, Gooley JJ, Saper CB, Digre K, 

Burstein R. A neural mechanism for exacerbation of headache by light. 

Nat Neurosci. Feb;13(2):239-45. 2010
Noseda R, Kainz V, Jakubowski M, Gooley JJ, 

Saper CB, Digre K, Burstein R. A neural mechanism 

for exacerbation of headache by light. Nat Neurosci. 

Feb;13(2):239-45. 2010
Noseda R, Kainz V, Jakubowski M, Gooley JJ, 

Saper CB, Digre K, Burstein R. A neural mechanism 

for exacerbation of headache by light. Nat Neurosci. 

Feb;13(2):239-45. 2010

? 
CGRP, Migraine and Photosensitivity

Calcitonin Gene-Related 

Peptide (CGRP) modulates 

trigeminal activity in the eye 

and brain

1.CGRP levels reported elevated 

in migraine

2.Injection of CGRP induces 

headache and photophobia

3.CGRP receptor antagonist 





State-of-Art Reviews, Section Editors: Grant T. Liu, MD and Randy H. Kardon, MD, PhD

Journal of Neuro-Ophthalmology, 2012;32:68-81, Shedding Light on Photophobia

Kathleen B. Digre, MD and K.C. Brennan, MD

Photophobia Circuit
The Photo-Blink Reflex

 Protects the eye after a bright flash1-4 

 

1.Mukuno K et al.. Jpn J 

Ophthalmol. 27(1):261-70. 

1983.

2.Malin JP. Elektroenzephalogr 

Elektromyogr Verwandte Geb. 

Sep;13(3):101-7. German. 

1982.

3.Yasuhara M, Naito H.. Int J 

Neurosci. Jul;17(1):23-31. 

1982.

4.Ozaki T.. Nippon Seirigaku 

Zasshi. 38(1):15-6. Japanese. 

1976.

5.Noseda R, Kainz V, 

Jakubowski M, Gooley JJ, 

Saper CB, Digre K, Burstein R. 

A neural mechanism for 

exacerbation of headache by 

light. Nat Neurosci. 

Feb;13(2):239-45. 2010
The Photo-Blink Reflex

 Protects the eye after a bright flash1-4

 Melanopsin containing retinal ganglion cells may mediate the 

afferent arm of this reflex through projections to the thalamus 

and trigeminal nucleus5 and may explain the paradoxical 

photosensitivity in patients blinded by photoreceptor loss5 

1. Mukuno K et al.. Jpn J Ophthalmol. 27(1):261-70. 1983.

2. Malin JP. Elektroenzephalogr Elektromyogr Verwandte Geb. Sep;13(3):101-7. German. 1982.

3. Yasuhara M, Naito H.. Int J Neurosci. Jul;17(1):23-31. 1982.

4. Ozaki T.. Nippon Seirigaku Zasshi. 38(1):15-6. Japanese. 1976.

5. Noseda R, Kainz V, Jakubowski M, Gooley JJ, Saper CB, Digre K, Burstein R. A neural 

mechanism for exacerbation of headache by light. Nat Neurosci. Feb;13(2):239-45. 2010
Poll Question 3

Of the patients you see with photosensitivity, 

which cause best characterizes the majority?

• 1) thought to be caused by Traumatic Brain Injury

• 2) thought to be a manifestation of migraine (can be 

during or between headaches)

• 3) related to ocular cause (e.g. uveitis, ocular trauma)

• 4) related to other brain disorder (e.g. post 

meningitis, tumor)
Poll Question 4

Of the patients you see with photosensitivity, 

which of the two choices best characterizes their 

light sensitivity?

• 1) everything seems too bright, but headache is not a 

major component of the symptom.

• 2) light causes headache or makes their headaches 

worse, but visually, the light does not seem brighter 

than normal
Photosensitivity Hypothesis

 Abnormal sensitivity of the trigeminal nerve and its 

recipient sensory brainstem nucleus

 A trigeminal brainstem reflex mediated by light 

would be exagerated in photosensitivity
Methods

 15 normal subjects and 12 patients with photosensitivity 

were tested using red (640nm) and blue (485nm) 

Ganzfeld light, one second in duration over a 6 log unit 

range of intensity (0.5 log unit steps).

 

 Time-stamped, computerized recording of the pupil, 

orbicularis and procerus muscle EMG, skin conductance 

and heart rate were measured simultaneously. 
Methods Light exposure Electromyography 

Pre-Stimulus Stimulus Post-Stimulus 
Photic-EMG Induced by Red and Blue Light

EMG Procerus Muscle

EMG Orbicularis Muscle

Time (sec)

Pieter Poolman, Randy Kardon

One second in duration, over 6 log unit range of intensity (0.5 log unit steps)
Photic-EMG Induced by Red & Blue Light (cont.)

EMG Procerus Muscle

EMG Orbicularis Muscle

Time (sec)

One second in duration, over 6 log unit range of intensity (0.5 log unit steps)

EMG RMS

Red Light

(640 nm)

EMG RMS

Blue Light

(485 nm)

Pieter Poolman, Randy Kardon
EMG and Pupil Responses to Different Red 

and Blue Light Intensities 

EMG RMS

Red Light

EMG RMS

Blue Light

Pupil Size

Red Light

Pupil Size

Blue Light
Photic-EMG Response Function

Does it Shift in Photophobia and in Migraine? EMG Procerus (Peak RMS)

Log Stimulus Light Intensity

blue light

red light
Pieter Poolman, Susan Anderson

Exaggerated EMG Responses in Patients 

with Photosensitivity

Red Light Stimuli Blue Light Stimuli
Brightness Sense vs Discomfort

Magnitude of Estimation

Blue Light
Brightness Sense vs Discomfort 

Normal vs TBI Patients

Red Light Blue Light

Salivary Calcitonin Gene Related Peptide 

(CGRP) Responses to Light
CGRP

Air puff

Photic-induced Orbicularis Oculi EMG Responses 

to Light and CGRP in Awake Mice 
CGRP

Air puff

Photic-induced Orbicularis Oculi EMG Responses 

to Light and CGRP in Awake Mice 
CGRP

Air puff

Photic-induced Orbicularis Oculi EMG Responses 

to Light and CGRP in Awake Mice 
Photic-induced Orbicularis Oculi EMG Responses 

to Light and CGRP in Awake Mice 

CGRP

Air puff
Exposure To Bright Light Increase Orbicularis 

Oculi EMG Activity in Chronically Implanted Mice
Air Puff Induced Blink Reflex: 

Accentuation by Light and CGRP

Dark Light

Dark + CGRP Puff Light + CGRP

Puff

Puff

Puff
Air Puff Induced Blink Reflex: 

Accentuation by Light and CGRP
Controlling Photophobia and Light-Induced Headache: 

The Use of Artificial Pupil Contact Lenses

Mary M. Jackowski1,3,4 and Brad C. Motter1,2 1VA Medical Center, Syracuse, NY; 2Neuroscience and Physiology, 3Ophthalmology, 4Physical 

Medicine and Rehabilitation SUNY Upstate Medical University, Syracuse , NY

Poll Question 5

Which treatment do patients feel is most helpful?

• 1) dark sunglasses

• 2) orange colored sunglasses

• 3) blue colored sunglasses

• 4) contact lenses with artificial pupils

• 5) miotic eye drops

• 6) medications used to treat migraine

• 7) nothing seems to help significantly
Conclusions

 Physiological evidence is provided in humans that photic-EMG 

responses are exaggerated in photosensitive patients

 The photic-blink reflex may be mediated by melanopsin containing 

retinal ganglion cells (MCGs)

 MGCs likely provide input to the trigeminal sensory nucleus, which 

stimulates the facial nucleus, as evidenced by EMG responses of 

orbicularis and procerus muscles

 CGRP may mediate excessive trigeminal sensory activation

 Treatment Options: CGRP antagonists, blue blocking lenses, 

occlusive contact lenses, pilocarpine
Funded by the Department of Veterans Affairs, 

and the US Department of Defense (TATRC)

Thank You!
Contact Information

email: randy-kardon@uiowa.edu

Department of Ophthalmology Website Faculty Profile for Randy Kardon:

https://www.medicine.uiowa.edu/dept_primary_apr.aspx?appointment=Opht

halmology%20and%20Visual%20Sciences&id=kardonr

Iowa City VA Center of Excellence for the Prevention and Treatment of Visual 

Loss Website:

http://www.vision.research.va.gov/