Neuro-

Ophthalmology
2015
Neuro-Ophthalmology
Made Ridiculously Simple
Program Directors
Michael S Lee MD and Prem S Subramanian MD PhD

In conjunction with the

North American Neuro-Ophthalmology Society
Sands Expo/Venetian
Las Vegas, Nevada

Saturday, Nov. 14, 2015

Presented by:
The American Academy of Ophthalmology

2015 Neuro-Ophthalmology Planning Group 2011 Andrew G Lee MD Staff

Michael S Lee MD 2009 Karl C Golnik MD Melanie R Rafaty CMP, Director, Scientific
Program Director Leah Levi MBBS Meetings
Prem S Subramanian MD PhD 2007 Andrew G Lee MD Ann L’Estrange, Scientific Meetings Specialist
Program Director Karl C Golnik MD Christa Fernandez, Presenter Coordinator
Debra Rosencrance CMP CAE, Vice
Anne S Abel MD Subspecialty Day Advisory Committee President, Meetings & Exhibits
Rudrani Banik MD William F Mieler MD Patricia Heinicke Jr, Copyeditor
Sophia Mihe Chung MD Associate Secretary Mark Ong, Designer
Sarita B Dave MD Gina Comaduran, Cover Design
Mays A El-Dairi MD Donald L Budenz MD MPH
Andrew G Lee MD Daniel S Durrie MD
Collin M McClelland MD Francis S Mah MD
Mitchell B Strominger MD R Michael Siatkowski MD
Nicolas J Volpe MD
Former Program Directors Jonathan B Rubenstein MD
2013 Andrew G Lee MD Secretary for Annual Meeting
Michael S Lee MD

©2015 American Academy of Ophthalmology. All rights reserved. No portion may be reproduced without express written consent of the American Academy of Ophthalmology.
ii  2015 Subspecialty Day  |  Neuro-Ophthalmology

2015 Neuro-Ophthalmology
Subspecialty Day Planning Group
On behalf of the American Academy of Ophthalmology and the North American Neuro-Ophthalmology Society (NANOS), it is our
pleasure to welcome you to Las Vegas and Neuro-Ophthalmology 2015: Neuro-Ophthalmology Made Ridiculously Simple.

Michael S Lee MD Prem Subramanian MD PhD

Program Director Program Director
Eli Lilly & Company: S NASA: C
Neuro-ophthalmix: E,P National Eye Institute: S
Novartis Pharmaceuticals Corp.: S
US Department of Defense: S

Program Planning Group

Anne S Abel MD Rudrani Banik MD Sophia Mihe Chung MD

None National Eye Institute: S Eli Lilly & Company: S
2015 Subspecialty Day  |  Neuro-Ophthalmology Subspecialty Day Planning Group iii

No photo No photo
available available

Sarita B Dave MD Andrew G Lee MD Mitchell B Strominger MD

New York State Department of CredentialProtection: O None
Health: S

Collin M McClelland MD
Mays A El-Dairi MD None
Prana Pharmaceuticals: C
2015 Subspecialty Day  |  Neuro-Ophthalmology  v

Neuro-Ophthalmology 2015 Contents

Program Planning Group  ii

CME vi

Faculty Listing  viii

Program Schedule  xiv

Section I: Vision Loss Made Ridiculously Simple  2, 28

Mini-Talk: How I Use Testing When I Suspect Optic Neuropathy  4

Advocating for Patients  8

Section II: Your “What” Hurts? Eye Pain and Headache Made Ridiculously Simple  10, 33

Mini-Talk: “Where Do I Begin?” Headache History and Exam Made Ridiculously Simple  12

Section III: Double Vision and Nystagmus Made Ridiculously Simple  15, 37

Mini-Talk: Orbital Pulleys and Muscles Made Ridiculously Simple  17

Section IV: Test Interpretation Made Ridiculously Simple  23, 42

Mini-Talk: Bias in Testing—Do I Only Find What I Thought Was There?  25

Faculty Financial Disclosure  47

Presenter Index  50
vi  2015 Subspecialty Day  |  Neuro-Ophthalmology

CME Credit

Academy’s CME Mission Statement Teaching at a Live Activity

The purpose of the American Academy of Ophthalmology’s Teaching instruction courses or delivering a scientific paper or
Continuing Medical Education (CME) program is to pres- poster is not an AMA PRA Category 1 Credit™ activity and
ent ophthalmologists with the highest quality lifelong learning should not be included when calculating your total AMA PRA.
opportunities that promote improvement and change in physi- Category 1 Credits™: Presenters may claim AMA PRA Cat-
cian practices, performance, or competence, thus enabling such egory 1 Credits™ through the American Medical Association.
physicians to maintain or improve the competence and profes- Please contact the AMA to obtain an application form at www.
sional performance needed to provide the best possible eye care ama-assn.org.
for their patients.
Scientific Integrity and Disclosure of Financial
2015 Neuro-Ophthalmology Subspecialty Day Interest
Meeting Learning Objectives
The American Academy of Ophthalmology is committed to
Upon completion of this activity, participants should be able to: ensuring that all CME information is based on the application
of research findings and the implementation of evidence-based
• Recognize urgent signs and symptoms in the evaluation of
medicine. It seeks to promote balance, objectivity, and absence of
adults with diplopia
commercial bias in its content. All persons in a position to con-
• Direct the initial workup of a patient with visual loss from
trol the content of this activity must disclose any and all financial
optic neuropathy
interests. The Academy has mechanisms in place to resolve all
• Distinguish the key findings in the management of eye pain
conflicts of interest prior to an educational activity being deliv-
and associated headache
ered to the learners.
• Determine when and how to order neuroimaging studies
The Academy requires all presenters to disclose on their first
for ophthalmic conditions
slide whether they have any financial interests from the past 12
months. Presenters are required to verbally disclose any financial
2015 Neuro-Ophthalmology Subspecialty Day interests that specifically pertain to their presentation.
Meeting Target Audience
The intended audience for this program is comprehensive oph- Attendance Verification for CME Reporting
thalmologists.
Before processing your requests for CME credit, the Academy
must verify your attendance at Subspecialty Day and/or at AAO
2015 Neuro-Ophthalmology Subspecialty Day 2015. In order to be verified for CME or auditing purposes, you
Meeting CME Credit must either:
The American Academy of Ophthalmology is accredited by the • Register in advance, receive materials in the mail, and turn
Accreditation Council for Continuing Medical Education to pro- in the Final Program and/or Subspecialty Day Syllabus
vide continuing medical education for physicians. exchange voucher(s) onsite;
The American Academy of Ophthalmology designates this • Register in advance and pick up your badge onsite if mate-
live activity for a maximum of 7 AMA PRA Category 1 Cred- rials did not arrive before you traveled to the meeting; or
its™. Physicians should claim only the credit commensurate with • Register onsite.
the extent of their participation in the activity.
CME Credit Reporting
ABO Self-Assessment Credit
Level 2; Academy Resource Center, Hall B, Booth 2632
This activity meets the Self-Assessment CME requirements
Attendees whose attendance has been verified (see above) at
defined by the American Board of Ophthalmology (ABO). Please
AAO 2015 can claim their CME credit online during the meet-
be advised that the ABO is not an accrediting body for purposes
ing. Registrants will receive an email during the meeting with a
of any CME program. The ABO does not sponsor this or any
link and instructions on how to claim credit. Onsite, you may
outside activity, and the ABO does not endorse any particular
report credits earned during Subspecialty Day and/or AAO 2015
CME activity. Complete information regarding the ABO Self-
at the CME Credit Reporting booth.
Assessment CME Maintenance of Certification requirements is
Academy Members: The CME credit reporting receipt is not a
available at http://abop.org/maintain-certification/part-2-life-
CME transcript. CME transcripts that include AAO 2015 cred-
long-learning-self-assessment/cme/.
its entered onsite will be available to Academy members on the
NOTE: Credit designated as “self-assessment” is AMA PRA
Academy’s website beginning Dec. 10, 2015.
Category 1 Credit™ and is also preapproved by the ABO for the
NOTE: CME credits must be reported by Jan. 13, 2016.
Maintenance of Certification (MOC) Part II CME requirements.
After AAO 2015, credits can be claimed at www.aao.org. The
2015 Subspecialty Day  |  Neuro-Ophthalmology CME Credit vii

Academy transcript cannot list individual course attendance. It

will list only the overall credits spent in educational activities at
Subspecialty Day and/or AAO 2015.
Nonmembers: The Academy will provide nonmembers with
verification of credits earned and reported for a single Academy-
sponsored CME activity, but it does not provide CME credit
transcripts. To obtain a printed record of your credits, you must
report your CME credits onsite at the CME Credit Reporting
booths.

Proof of Attendance
The following types of attendance verification will be available
during AAO 2015 and Subspecialty Day for those who need it
for reimbursement or hospital privileges, or for nonmembers
who need it to report CME credit:
• CME credit reporting/proof-of-attendance letters
• Onsite registration receipt
• Instruction course and session verification
Visit www.aao.org for detailed CME reporting information.
viii  2015 Subspecialty Day  |  Neuro-Ophthalmology

Faculty

Anne S Abel MD Rudrani Banik MD Valerie Biousse MD

Wayzata, MN New York, NY Atlanta, GA
Neuro-Ophthalmologist Associate Adjunct Surgeon Professor of Ophthalmology and
Hennepin County Medical Center, The New York Eye & Ear Infirmary Neurology
Minneapolis, MN Associate Professor of Ophthalmology Emory University School of Medicine
New York Medical College

No photo
available

Marie D Acierno MD Gabrielle R Bonhomme MD

Baton Rouge, LA Jeffrey Bennett MD PhD Pittsburgh, PA
Professor of Ophthalmology Aurora, CO Assistant Professor of Ophthalmology
Residency Director of Ophthalmology Professor of Neurology and University of Pittsburgh
LSU Health Sciences Center/Ochsner, Ophthalmology M.D.
New Orleans University of Colorado School of University of Pittsburgh Medical Center
Medicine

Anthony C Arnold MD Michael C Brodsky MD

Los Angeles, CA M Tariq Bhatti MD Rochester, MN
Professor and Chief Durham, NC Professor of Ophthalmology and
Neuro-Ophthalmology Division Professor of Ophthalmology and Neurology
Jules Stein Eye Institute Neurology Mayo Clinic
Duke University Eye Center and Duke
University Medical Center
2015 Subspecialty Day  |  Neuro-Ophthalmology Faculty Listing ix

No photo
available

John J Chen MD Sarita B Dave MD Marc J Dinkin MD

Rochester, MN Jersey City, NJ New York, NY
Assistant Professor Neuro-Ophthalmologist, ECRIP Assistant Professor of Ophthalmology
Mayo Clinic Investigator and Director of Neuro-
New York Eye and Ear Infirmary of Ophthalmology
Mount Sinai Weill Cornell Medical College, NY
Presbyterian Hospital
Clinical Affiliate
Memorial Sloan Kettering Cancer Center

Sophia Mihe Chung MD

St Louis, MO
Professor of Ophthalmology, Neurology Joseph L Demer MD PhD
& Psychiatry, and Neurosurgery Los Angeles, CA
Saint Louis University School of Leonard Apt Professor of
Medicine Ophthalmology Mays A El-Dairi MD
Professor of Neurology Durham, NC
David Geffen Medical School Assistant Professor
University of California, Los Angeles Duke Eye Center
Director of Ocular Motility Laboratory
Stein Eye Institute
University of California, Los Angeles

Fiona E Costello MD
Calgary, AB, Canada
Associate Professor
Department of Clinical Neurosciences Rod Foroozan MD
and Surgery Houston, TX
University of Calgary, Hotchkiss Brain Associate Professor of Ophthalmology
Institute Kathleen B Digre MD Baylor College of Medicine
Clinician-Scientist Salt Lake City, UT
Hotchkiss Brain Institute Professor, Neurology and
Ophthalmology
Moran Eye Center
University of Utah
x Faculty Listing 2015 Subspecialty Day  |  Neuro-Ophthalmology

Courtney E Francis MD Gena Heidary MD Bradley J Katz MD

Seattle, WA Cambridge, MA Salt Lake City, UT
Assistant Professor Director, Pediatric Neuro Associate Professor of Ophthalmology
Department of Ophthalmology Ophthalmology Service and Neurology
University of Washington Boston Children’s Hospital University of Utah
Assistant Professor in Ophthalmology
Harvard Medical School

Todd A Goodglick MD Lanning B Kline MD

Chevy Chase, MD Birmingham, AL
Department of Ophthalmology Guy V Jirawuthiworavong MD Professor of Ophthalmology
Georgetown University/Washington Torrance, CA University of Alabama at Birmingham
Hospital Center Regional Neuro-Ophthalmologist
Washington Eye Physicians Uveitis Consultant & Medical
Retinologist
Southern California Kaiser Permanente
Medical Group

Gregory S Kosmorsky DO
Highland Heights, OH
Lynn K Gordon MD PhD Head, Section of Neuro-Ophthalmology
Los Angeles, CA Cleveland Clinic
Professor of Ophthalmology
Jules Stein Eye Institute, David Geffen Randy H Kardon MD PhD
School of Medicine Iowa City, IA
University of California, Los Angeles Professor of Ophthalmology and
Senior Associate Dean, Diversity Affairs Director of Neuro-Ophthalmology
David Geffen School of Medicine University of Iowa
University of California, Los Angeles Professor of Ophthalmology
Director, Center for Prevention &
Treatment of Visual Loss
Surgery and Research Division
Department of Veterans Affairs
2015 Subspecialty Day  |  Neuro-Ophthalmology Faculty Listing xi

Jacqueline A Leavitt MD Leah Levi MD Neil R Miller MD

Rochester, MN La Jolla, CA Baltimore, MD
Consultant Director of Neuro-Ophthalmology Frank B Walsh Professor of Neuro-
Mayo Clinic Scripps Clinic Division of Ophthalmology
Associate Professor of Ophthalmology Ophthalmology Wilmer Eye Institute
Mayo Medical School Johns Hopkins University School of
Medicine
Professor of Ophthalmology, Neurology
and Neurosurgery
Johns Hopkins University School of
Medicine

Grant T Liu MD
Andrew G Lee MD Philadelphia, PA
Houston, TX Neuro-Ophthalmology Service
Professor of Ophthalmology, Neurology, Division of Ophthalmology
and Neurosurgery Children’s Hospital of Philadelphia
Weill Cornell Medical College Division of Neuro-Ophthalmology,
Chairman of Ophthalmology Department of Neurology Heather Moss MD PhD
Houston Methodist Hospital, Blanton Hospital of the University of Chicago, IL
Eye Institute Pennsylvania Assistant Professor of Ophthalmology
and Visual Sciences
Clinical Assistant Professor of Neurology
and Rehabilitation
University of Illinois at Chicago

Michael S Lee MD Collin M McClelland MD

Minneapolis, MN Saint Louis, MO
Professor, Departments of Assistant Professor of Neuro-
Ophthalmology, Neurology and Ophthalmology
Neurosurgery Department of Ophthalmology Nancy J Newman MD
University of Minnesota Washington University in St. Louis Atlanta, GA
LeoDelle Jolley Professor of
Ophthalmology
Professor of Ophthalmology and
Neurology
Emory University School of Medicine
xii Faculty Listing 2015 Subspecialty Day  |  Neuro-Ophthalmology

No photo No photo
available available

Jeffrey G Odel MD John Pula MD Alfredo A Sadun MD PhD

New York, NY Chicago, IL Pasadena, CA
Professor of Ophthalmology Clinician, Northshore University F Thornton Chair
Columbia University Medical Center Healthsystem Department of Ophthalmology
Associate Professor Doheny Eye Institute
University of Chicago College of University of California, Los Angeles
Medicine

Paul H Phillips MD
Little Rock, AR
Professor of Ophthalmology Peter J Savino MD
University of Arkansas for Medical Jacinthe Rouleau MD La Jolla, CA
Sciences Montreal, QC, Canada Professor of Neuro-Ophthalmology
Chief-of-Staff Clinical Assistant Professor and Chief, Shiley Eye Institute
Department of Ophthalmology Neuro-Ophthalmology Section University of California, San Diego
Arkansas Children’s Hospital Université de Montréal

No photo
available

Harold E Shaw Jr MD
Stacy L Pineles MD Janet C Rucker MD Greenville, SC
Los Angeles, CA New York, NY Practicing Ophthalmologist
Assistant Professor of Ophthalmology Associate Professor of Neurology Jervey Eye Group, P.A.
University of California, Los Angeles New York University School of Clinical Assistant Professor
Medicine University of South Carolina School of
Medicine - Greenville
2015 Subspecialty Day  |  Neuro-Ophthalmology Faculty Listing xiii

No photo
available

S Tonya Stefko MD Prem S Subramanian MD PhD Nicholas J Volpe MD

Gibsonia, PA Baltimore, MD Chicago, IL
Assistant Professor of Ophthalmology Professor of Ophthalmology, Neurology, George and Edwina Tarry Professor of
and Neurological Surgery and Neurosurgery Ophthalmology and Chairman
University of Pittsburgh Medical Center University of Colorado School of Feinberg School of Medicine
Medicine Northwestern University
Associate Professor of Surgery
Uniformed Services University of the
Health Sciences

No photo
available

Mitchell B Strominger MD
Boston, MA Kimberly M Winges MD
Professor of Ophthalmology and Portland, OR
Pediatrics Neuro-Ophthalmologist
Tufts University School of Medicine Gregory P Van Stavern MD Veterans Affairs Health System
St Louis, MO Assistant Professor of Ophthalmology
Associate Professor and Neurology
Department of Ophthalmology and Casey Eye Institute
Visual Sciences Oregon Health and Sciences University
Washington University in St. Louis
xiv Program Schedule 2015 Subspecialty Day  |  Neuro-Ophthalmology

Neuro-Ophthalmology Subspecialty Day 2015:

Neuro-Ophthalmology Made Ridiculously Simple
In conjunction with the North American Neuro-Ophthalmology Society
(NANOS)
Saturday, Nov. 14
7:00 AM CONTINENTAL BREAKFAST
8:00 AM Welcome and Introductions Michael S Lee MD*

Section I: Vision Loss Made Ridiculously Simple

Moderators: Sophia Mihe Chung MD*, Mays A El-Dairi MD*
Panelists: Lynn K Gordon MD PhD*, Jacqueline A Leavitt MD, Grant T Liu MD, Neil R Miller MD*
8:05 AM “I suddenly lost vision in one eye.” Marie D Acierno MD 2, 28
8:20 AM “I’m slowly losing vision in one of my eyes.” Guy V Jirawuthiworavong
MD 2, 29
8:35 AM “My doctor says I might have glaucoma.” Jacinthe Rouleau MD 3, 30
8:50 AM Mini-Talk: How I Use Testing When I Suspect Optic Neuropathy Alfredo A Sadun MD PhD* 4
9:00 AM “I lose my vision and then it comes back.” Jeffrey Bennett MD PhD 6, 31
9:15 AM “I am losing vision in both eyes.” John J Chen MD 6, 31
9:30 AM “Can my child see?” Gena Heidary MD* 7, 32
9:40 AM Recap Prem S Subramanian MD PhD*
9:50 AM Advocating for Patients Lynn K Gordon MD PhD*  8
9:55 AM REFRESHMENT BREAK and AAO 2015 EXHIBITS

Section II: Your “What” Hurts? Eye Pain and Headache Made Ridiculously Simple
Moderators: Andrew G Lee MD*, Anne S Abel MD
Panelists: Kathleen B Digre MD, Lanning B Kline MD, Gregory S Kosmorsky DO, Nicholas J Volpe MD
10:25 AM “Worst headache of my life!” S Tonya Stefko MD 10, 33
10:40 AM “My head hurts for days on end...” John Pula MD 10, 33
10:55 AM “My eye just aches all the time.” Rod Foroozan MD* 11, 34
11:10 AM Mini-Talk: “Where Do I Begin?” Headache History and Exam Made Lynn K Gordon MD PhD* 12
Ridiculously Simple
11:20 AM “The light!! It hurts my eyes!!” Bradley J Katz MD* 14, 35
11:35 AM “It hurts when I talk, and this cough won’t go away.” Gabrielle R Bonhomme MD 14, 36
11:50 AM Recap Michael S Lee MD*
11:55 AM LUNCH and AAO 2015 EXHIBITS

* Indicates that the presenter has financial interest.

No asterisk indicates that the presenter has no financial interest.
2015 Subspecialty Day  |  Neuro-Ophthalmology Program Schedule xv

Section III: Double Vision and Nystagmus Made Ridiculously Simple

Moderators: Mitchell B Strominger MD, Sarita B Dave MD
Panelists: Michael C Brodsky MD, Leah Levi MD, Nancy J Newman MD, Peter J Savino MD
1:10 PM “I see double and my eyelid is in the way.” Paul H Phillips MD 15, 37
1:25 PM “I see two golf club heads when I putt.” Courtney E Francis MD 15, 38
1:40 PM “Things are blurry and jumpy when I read.” Janet C Rucker MD 16, 38
1:55 PM Mini-Talk: Orbital Pulleys and Muscles Made Ridiculously Simple Joseph L Demer MD PhD* 17
2:05 PM “Words run together on the TV.” Kimberly M Winges MD 21, 39
2:20 PM “I see double when I get tired.” Marc J Dinkin MD 22, 39
2:35 PM “I see double after my cataract surgery.” Stacy L Pineles MD 22, 41
2:50 PM Recap Michael S Lee MD*
2:55 PM REFRESHMENT BREAK and AAO 2015 EXHIBITS

Section IV: Test Interpretation Made Ridiculously Simple

Moderators: Rudrani Banik MD*, Collin M McClelland MD
Panelists: Anthony C Arnold MD*, Valerie Biousse MD*, Randy H Kardon MD PhD*, Jeffrey G Odel MD
3:25 PM What Do I Do With This Visual Field? Gregory P Van Stavern  23, 42
3:40 PM Should I Trust My Exam, or the OCT? M Tariq Bhatti MD* 23, 43
3:55 PM I Can’t Get Cocaine Drops in My Office! Heather Moss MD PhD* 24, 44
4:10 PM Mini-Talk: Bias in Testing—Do I Only Find What I Thought Was There? Harold E Shaw Jr MD* 25
4:20 PM The MRI Is Abnormal—Now What? Fiona E Costello MD* 26, 44
4:35 PM Everyone’s ESR Is High—Who Needs a Biopsy? Todd A Goodglick MD 26, 45
4:50 PM Recap Prem S Subramanian MD PhD*
4:55 PM Closing Remarks Prem S Subramanian MD PhD*
4:57 PM ADJOURN

* Indicates that the presenter has financial interest.

No asterisk indicates that the presenter has no financial interest.
Case Presentations
2 Section I: Vision Loss 2015 Subspecialty Day  |  Neuro-Ophthalmology

Section I: Vision Loss Made Ridiculously Simple

“I suddenly lost vision in one eye.” “I am slowly losing vision in one of

Marie D Acierno MD my eyes.”
Guy V Jirawuthiworavong MD
C ase
C ase
History and Exam
Twenty-year-old male reports left eye dull pain with eye move- History and Exam
ments and a constant headache that began one week ago. Several Fifty-three-year-old automotive saleswoman noted unilateral,
days later he noticed blurred vision in his left eye. The vision progressive loss of vision in the right eye over the last year. Her
gradually worsened over 1 to 2 days. He denies any involvement visual problems began in her early 20s, when she experienced
in the other eye. He has had no recent viral-like illness or associ- flashes of lights and “blank spots” in her vision. Multiple eye
ated symptoms. His past medical history is noncontributory. On examinations were unrevealing. A few years ago, she noted more
examination, his visual acuity is 20/20 O.D. and 20/80 O.S. with flashes, numerous dots, and a kaleidoscope of colors in her vision
a left relative afferent pupillary defect, dyschromatopsia, and a with more significant progression over the past 6 months. She
left central scotoma. Slitlamp biomicroscopy and IOPs are nor- was discovered to have a visual field defect by a retina specialist
mal. The funduscopic examination reveals a normal appearing 3 years ago, but records were not available. She was uncertain
right optic disc and left optic disc edema. There are no macular about a prior diagnosis of retinitis pigmentosa. She complains of
lesions, and the vitreous is clear in either eye. difficulty seeing at night and photophobia.
Past medical history is significant for fibromyalgia, eczema,
Clinical Course and Outcome anxiety, and depression. Family history is significant for glau-
coma in her late father, who “died of arthritis,” and ulcerative
The patient had an MRI brain/orbit imaging study with gadolin- colitis in her son. She denies family members needing a white
ium with fat suppression revealing enhancement of the left optic cane or a seeing eye dog. Review of systems reveals an occasional
nerve. His pain with eye movements began to subside shortly headache and Raynaud phenomenon that she describes as pain-
after clinical presentation. The patient received a 3-day course fully cold fingers. She denies any numbness or weakness. Her
of IV steroids at an outpatient infusion center. His vision in the current medications are tramadol, alprazolam, and citalopram.
left eye was 20/30 at 4 weeks after the onset, with subjective On examination, patient is a mild hyperope with BCVA of
improvement in his color vision. At 6 months, his visual acuity 20/25 O.D. and 20/20 O.S. Color vision is intact. She has a 2+
was 20/20 in each eye with no apparent relative afferent pupil- afferent pupillary defect on the right. Her confrontational fields
lary defect, subtle left optic disc atrophy, and retinal nerve fiber reveal a temporal defect in the right eye and a normal field in
layer thinning by OCT in the left eye compared to the right eye. the left eye. Her slitlamp exam is unremarkable. On fundus
exam, peripapillary atrophy with a cup-to-disc ratio of 0.3 O.U.
is noted. In the peripheral retina, sectoral pigmentary epithelial
atrophy, contiguous with the optic nerve, is seen, but there is
minimal, if any, bone spiculing. Amsler grid shows an incomplete
pericentral visual field defect temporal to fixation O.D. and no
defects O.S. A visual field is completed.

Clinical Course and Outcome

OCT macula and nerve fiber layer and an ultrawide-field fluo-
rescein angiogram were completed. Extensive blood testing for
infectious and inflammatory conditions did not reveal any con-
tributory findings. Old records were still in the process of being
obtained. The visual field in the right eye showed a “c-shaped”
pericentral zonal visual field defect that corresponded to the
perifoveal zonal retinal thinning of the macula on the OCT.
The left eye visual field had a mild enlarged blind spot, with the
OCT of the NFL being thinner on the left than on the right. The
fluorescein angiogram of the right eye showed zonal / sectoral
window defects extending superiorly and in continuity from the
optic disc, and the left eye had peripapillary retinal pigment epi-
thelial abnormalities with window defects. Watchful observation
2015 Subspecialty Day  |  Neuro-Ophthalmology Section I: Vision Loss 3

was recommended. Patient’s visual field remained stable, with metric IOP, visual acuity less than 20/40, and patient younger
sequential 30-2 and 10-2 visual field testing. Patient was assured than 50 years of age.
of the findings and that her condition was consistent with acute Because compressive or infiltrative lesions of the optic nerve
zonal occult outer retinopathy (AZOOR). She used tinted glasses can mimic visual field loss from glaucoma, neuroimaging, prefer-
to help decrease her photophobia. ably MRI of the brain and orbits with gadolinium contrast and
fat suppression, is warranted in any suspicious or atypical pre-
sentation.
In our case, some clues raise the suspicion for a nonglauco-
matous optic neuropathy. The optic disc demonstrates promi-
“My doctor says I might have nent pallor with less severe excavation and notching than in
glaucoma.” glaucoma. Moreover, the severity of the visual field loss inferi-
orly does not match the degree of the notching superiorly. The
Jacinthe Rouleau MD presence of the RAPD and the asymmetry in visual acuity also
raise suspicion, especially with the absence of asymmetric IOP
C ase
or pachymetry. In addition, the decreased color vision O.S. is
another red flag for a neuro-ophthalmologic pathology. Alter-
natively, the presence of structural crowding of the contralateral
History and Exam
disc (disc at risk of 0.2) and systemic hypertension and hyper-
A 75-year-old male is referred by his family doctor for suspicion lipidemia favor the diagnosis of an old nonarteritic anterior
of glaucoma because his confrontation visual field is abnormal ischemic optic neuropathy (NAION). Other potential risk fac-
inferiorly in the left eye. tors are diabetes, sleep apnea, generalized hypoperfusion, severe
The patient complains about a vague sensation of blurry anemia, nocturnal hypotension, and medications (amiodarone
vision in the left eye present for 4 months. He can’t remember and erectile dysfunction agents). Previous ischemic optic neu-
exact onset but it’s now stable. He has no headache or other neu- ropathy may present with nerve fiber bundle field loss and optic
rological symptoms. Three months ago an optometrist told him atrophy if seen after the disc swelling resolves. Increased cupping
that his visual field was abnormal O.S. and recommended that can be seen as sequelae of both arteritic and nonarteritic forms of
he see an ophthalmologist. However, the patient failed to do so, ischemic optic neuropathy, although it is more often seen in the
discussing his eye problem with his general practitioner instead. arteritic form.
His past medical history is significant for hypertension, hyper- In our case, the diagnosis of arteritic anterior ischemic optic
lipidemia, and cardiac stenting 4 years ago. His medications neuropathy is unlikely given the normal blood tests and the
include lisinopril, metoprolol, atorvastatin, aspirin, and clopido- absence of systemic symptoms of giant cell arteritis (headache,
grel. He is a nonsmoker. His family history is positive for a sister jaw claudication, weight loss, anorexia, or fever). NAION con-
with glaucoma. stitutes 95% of all anterior ischemic optic neuropathies and is
On examination, his BCVA is 20/25 O.D. and 20/40 O.S. the most common cause of acute optic neuropathy in people over
IOP is 21 in both eyes, with pachymetry of 537 and 542 microns the age of 50. Because of its prevalence, previously undiagnosed
O.D. and O.S., respectively. A relative afferent pupillary defect NAION with optic atrophy can be seen on routine ophthalmo-
(RAPD) is present O.S. Ocular motility is full. Anterior segment logic exam. When prior NAION is suspected, efforts should be
is normal except for moderate nuclear sclerosis in both eyes. made to document the acute initial disc edema by reviewing prior
Gonioscopy reveals open angles in both eyes. Color vision is medical records. In our case, acute optic disc swelling is docu-
decreased O.S. with HRR plates (O.D. 10/10 and 5.5/10 O.S). mented on the fundus pictures taken 3 months ago by his optom-
Visual field testing is normal O.D., but there is an inferior alti- etrist and confirms our diagnosis.
tudinal visual field defect O.S. Examination of the optic nerves Other causes of nonglaucomatous cupping include methanol
showed asymmetric cup-to-disc ratios. The maculae and periph- poisoning or genetic optic neuropathies like Leber hereditary
eral retina are normal. optic neuropathy (LHON) or dominant optic atrophy (DOA).
These are bilateral optic neuropathies with typically central
visual fields defects with profound optic atrophy. LHON is more
Clinical Course and Outcome
likely to present as sequential bilateral optic neuropathy, while
The cup-to-disc ratio of the right optic nerve is 0.2, while the left the methanol poisoning and DOA have relatively symmetric
is 0.5 with suspicion of pallor superiorly. OCT shows asymmet- involvement of the optic nerves.
ric cupping, and the left eye has thinning of the nerve fiber layer Additionally, in the presence of altitudinal field defect, a
superiorly and temporally. complete examination of the posterior pole and peripheral retina
MRI of brain and orbits with gadolinium, obtained by his is always important to rule out retinal pathology such as retinal
family doctor, was normal 2 weeks previously. Complete blood detachment or branch retinal vein or artery occlusion.
count, erythrocytes sedimentation rate, and C-reactive protein
were also normal.
Various causes of optic neuropathy can be mistaken for glau-
coma: compressive \ infiltrative, ischemic (both arteritic and non-
arteritic), congenital, hereditary, post-traumatic, demyelinating,
or toxic. Some red flags should raise suspicion for nonglaucoma-
tous cupping: pallor of the remaining rim, vertically aligned field
defects or other atypical visual fields defects for glaucoma (cen-
tral or cecocentral), marked RAPD, asymmetrical loss of color
vision, asymmetric cupping, especially without history of asym-
4 Section I: Vision Loss 2015 Subspecialty Day  |  Neuro-Ophthalmology

Mini-Talk: How I Use Testing When I Suspect

Optic Neuropathy
Alfredo A Sadun MD PhD

Neuro-ophthalmology is about getting a good history. This is Is there nerve fiber layer thinning or thickening, and does
not so much an exercise in compulsive detail as it is in asking the the macula have any abnormalities? None of these findings
right question, one that enables the clinician to test the hypoth- were evident.
esis. Hence, the best history is obtained by knowing the general
3. Visual field pattern
principles of neuro-ophthalmology, applying critical aspects
Are the central scotomas symmetrical? Is there respect for
of anatomy and physiology, and having a clear understanding
the vertical or horizontal raphes? In this case, small central
of the differential diagnosis. This differential diagnosis begins
scotomas crossing both the horizontal and vertical raphes
broadly and proceeds to the narrow based on answers to the
were seen.
questions posed. In particular, in cases of possible optic neuropa-
thy, the following questions are most important: In this patient, the pupils were normal; there was no APD.
And there was no optic disc edema or frank optic atrophy,
1. Does the patient see things as dark (brown or grey) as
though there was perhaps slight temporal pallor. The macular
opposed to distorted or blurred?
reflex was normal. These findings are consistent with the diag-
Loss of retinal ganglion cells (RGCs) or their axons in the
noses of parasellar mass, metabolic and non-organic, considered
optic nerve decreases the sense of brightness. In contra-
above. Non-organic vision loss should not be a diagnosis of
distinction, maculopathies often cause metamorphopsia,
exclusion. There are several tests that can help us find deliberate
problems with the ocular media, and refractive problems,
malingering and even evidence of conversion reaction hysteria.
blurred vision.
An intracranial mass, especially in the area of the chiasm, can be
2. Is there a subjective loss of color vision? easily found by neuroimaging. However, the visual acuities were
Dyschromatopsia is frequently the seminal symptom in worse than 20/400 O.U., unlikely to be seen in a chiasmal syn-
optic neuropathies. drome. Furthermore, the visual fields showed scotomas in both
the nasal and temporal side. Further questioning revealed that
If the answers to questions 1 and 2 are positive, assume that
the patient was not currently on any known toxic agent and had
there is an optic neuropathy. Most optic neuropathies are isch-
a good diet. How then to proceed with specialized testing?
emic, inflammatory, compressive, or metabolic.
1. HVF 30-2 vs. 10-2
3. What is the tempo or cadence of visual loss?
The 24-2 program is good for glaucoma screening and
Vascular injuries come on abruptly. Inflammatory condi-
monitoring. But the 30-2 gives a better indication of how
tions are more likely to be subacute. Metabolic and com-
the defect may emerge from the blind spot, and the 10-2 is
pressive injuries are likely to progress slowly.
good for detailing the shape of the central scotoma.
4. Is the condition unilateral or bilateral?
2. Red Amsler grid testing
Unless there is a chiasmal or postchiasmal lesion, bilateral
This is especially useful when the central scotoma is small
conditions speak to metabolic and, less likely, inflamma-
and shallow. Testing for both red and contrast in the
tory conditions.
central area can be very helpful in toxic / metabolic optic
If the answers to 3 and 4 suggest slow progressive bilateral neuropathies.
loss of vision, then the main differential diagnosis is between
3. OCT for macula, retinal nerve fiber layer (RNFL) and
a parasellar mass and metabolic optic neuropathy. But non-
ganglion cell layer (GCL)
organic vision loss should always be considered, especially in the
The RNFL showed slight thinning temporally O.U. But
absence of signs. Other useful questions include pain, pain with
OCT is not very sensitive for the RNFL in this quadrant.
eye movements, and other, especially neurological, associated
More obvious was thickening of the RNFL in the inferior
symptoms.
temporal areas O.U. The macula was clear of any cysts,
Let us assume, at this stage, that we have a 68-year-old
edema, or structural alterations. However the GCL was
woman with painless loss of vision characterized first by loss of
bilaterally and symmetrically thinned.
color, who sees a dark splotch in the center of her vision bilater-
ally. The visual loss came on over a period of several months. 4. MRI, etc.
But the referring physician did not note abnormalities on fundus In this case, MRI or other neuroimaging would not be that
examination. What should we concentrate on in the neuro-oph- helpful. Getting unnecessary imaging opens the Pandora’s
thalmological examination? Key elements in this examination box for both false positives and, more importantly, hyper-
are the following: diagnosis (real lesions that have no bearing on the patient’s
symptoms). Unwarranted anxiety, additional testing,
1. Pupils
biopsies, and even neurosurgical interventions have been
Are the reactions sluggish? Is there an afferent pupillary
known to follow MRIs that should not have been ordered
defect (APD)? In this case, no.
insofar as an intracranial lesion was already outside the
2. Optic disc appearance on fundus examination confines of the differential diagnosis.
Is there subtle evidence of disc edema, papillitis, telangi-
ectasis of peripapillary vessels, or arteriolar attenuation?
2015 Subspecialty Day  |  Neuro-Ophthalmology Section I: Vision Loss 5

In the aggregate, bilateral GCL thinning, especially in the set- Selected Readings
ting of RNFL thickening inferior temporally, is highly specific 1. Sadun AA. Mitochondrial optic neuropathies. J Neurol Neurosurg
for mitochondrial optic neuropathy. While the papillomacular Psychiatry. 2002; 72(4):423-425.
bundle is poorly visualized by OCT RNFL, GCL thickness in the
macula, especially in comparison to RNFL thickness, provides 2. Sadun A. Acquired mitochondrial impairment as a cause of optic
nerve disease. Trans Am Ophthalmol Soc. 1998; 96:881-923.
very helpful information in the detection, characterization, and
monitoring of both genetic and acquired forms of mitochondrial 3. Zoumalan CI, Sadun AA. Optical coherence tomography can moni-
optic neuropathies. This was demonstrated in glaucoma and, tor reversible nerve-fibre layer changes in a patient with ethambu-
more recently, in both genetic and acquired forms of mitochon- tol-induced optic neuropathy. Br J Ophthalmol. 2007; 91(6):839-
drial optic neuropathy. 840.
In the case described above, the patient had been on etham- 4. Barboni P, Savini G, Valentino ML, Montagna P, Cortelli P, De
butol for about 6 months when she first noted vision loss. Her Negri AM, Sadun F, Bianchi S, Longanesi L, Zanini M, de Vivo A,
dosing was too high, especially in light of her compromised Carelli V. Retinal nerve fiber layer evaluation by optical coherence
kidney function (creatinine of 1.4). Her ophthalmologist discon- tomography in Leber’s hereditary optic neuropathy. Ophthalmol-
tinued the ethambutol, but the vision loss progressed such that ogy 2005; 112(1):120-126.
by 8 months, her vision fell to counting fingers O.U. It was then 5. Barboni P, Savini G, Cascavilla ML, Caporali L, Milesi J, Borrelli
that she presented to us not “currently” on any toxic medica- E, La Morgia C, Valentino ML, Triolo G, Lembo A, Carta A, De
tion. However, persistent or even progressively worsening vision Negri A, Sadun F, Rizzo G, Parisi V, Pierro L, Bianchi Marzoli S,
after discontinuation of therapy is not uncommon in ethambutol Zeviani M, Sadun AA, Bandello F, Carelli V. Early macular retinal
toxicity, which is an acquired form of mitochondrial optic neu- ganglion cell loss in dominant optic atrophy: genotype-phenotype
ropathy. The patient began to recover at 9 months and returned correlation. Am J Ophthalmol. 2014; 158(3):628-636.
to 20/25 after 1-2 years.
This case serves to remind us of the value of history tak-
ing in neuro-ophthalmology. History related to her past MAC
infection, ethambutol dosing, and her kidney functions were all
obtained with the knowledge that slowly progressive bilaterally
symmetrical optic neuropathies are often metabolic. Genetic and
acquired causes can often be determined by a judicious history,
aided by the limited use of precise testing modalities. Choosing
to obtain OCT for RNFL and GCL measures proved much more
useful than neuro-imaging.
6 Section I: Vision Loss 2015 Subspecialty Day  |  Neuro-Ophthalmology

“I lose my vision and then it comes “I’m losing vision in both eyes.”
back.” John J Chen MD
Jeffrey Bennett MD PhD
C ase
C ase
History and Exam
History and Exam A 54-year-old female with a 2-year history of normal-tension
A 57-year-old woman presented with a 1-month history of tran- glaucoma was referred for bilateral progressive visual loss. One
sient, painless vision loss in the right eye. The episodes lasted year prior to presentation, she developed painless, progressive
an average of 5-10 minutes, but some lasted longer. The events vision loss in the left eye that kept progressing despite cataract
typically began with flashing lights and progressed to light per- surgery. This prompted bilateral trabeculectomies with single-
ception vision. The episodes occurred sporadically and in rare digit IOP outcomes. However, she continued to develop painless,
instances happened more than once in a single day. There were progressive vision loss in the right eye 6 months later, which led
no concurrent ophthalmologic or neurologic symptoms. Between to a referral to neuro-ophthalmology for further evaluation.
events, the vision in her right eye remained slightly blurred. The The patient was no longer able to work as a nurse or drive.
patient’s past medical history was notable for hypertension, and Other than the vision loss, she was asymptomatic. Her past
her current medications included enalapril and estrogen. Fam- medical history is significant for hyperlipidemia and depression.
ily and social history were unremarkable. Review of systems Medications include simvastatin and sertraline.
revealed no fevers, chills, night sweats, temporal artery tender- On examination, BCVA was CF O.D. and HM O.S. There
ness, polymyalgia, or jaw claudication. was a 2.1 log unit relative afferent pupillary defect O.S. IOPs
On examination, visual acuities were 20/30 right eye and were 1 O.D. and 6 O.S. (mmHg). Slitlamp examination showed
20/20 left eye, with subjective color desaturation in the right eye. a large elevated bleb superiorly O.U., mild cataract O.D., and
Visual fields were full, and pupils were briskly reactive to light pseudophakia O.S. Fundus examination revealed a cup-to-disc
without an afferent pupillary defect. Motility was normal and ratio of 0.9 O.D. and 0.95 O.S.
dilated exam showed no evidence of optic disc or retinal abnor-
malities. Clinical Course and Outcome
Goldmann visual fields showed dense central scotoma and nasal
Clinical Course and Outcome loss, bilaterally. OCT showed severe thinning of the retinal nerve
Following the fundus examination, the patient experienced an fiber layer O.U. with mild chorioretinal folds O.D. Detailed fun-
episode of vision loss in the right eye. Visual acuity dropped dus examination revealed pallor of the remaining rim O.S.
to light perception in the right eye, and the right pupil dilated The patient underwent an MRI that showed a large sel-
slightly and became sluggishly reactive to light with an associated lar mass with compression of the chiasm and optic nerves.
right afferent defect. Fundus exam showed constriction of retinal She underwent bifrontal craniotomy 1 week later with gross
arterioles with sluggish flow in retinal bed and segmental con- resection revealing a WHO grade II chordoid meningioma.
striction of retinal veins with “box-carring.” She noticed instant improvement in the vision O.D. following
Subsequent laboratory studies showed a normal complete the surgery. Examination 2 months later showed her vision
blood count, erythrocyte sedimentation rate, C-reactive protein, improved from CF to 20/60 O.D. O.S. remained HM. Visual
and comprehensive metabolic profile. Serology was negative for fields showed a prominent nasal step consistent with underlying
antinuclear antigen and anti-neutrophil cytoplasmic antibody. glaucoma.
MRI brain and MR angiography of the neck were normal. Echo-
cardiography showed normal function, and bubble study was
negative.
The patient was treated with verapamil and had no further
events.
2015 Subspecialty Day  |  Neuro-Ophthalmology Section I: Vision Loss 7

“Can my child see?” Exam

Vision: Light averse in each eye. No response to 20/2400 card
Gena Heidary MD PhD on preferential looking testing and unable to elicit response to
the optokinetic nystagmus drum. Cycloplegic refraction was
C ase +1.50 sphere in each eye. Sensorimotor exam was notable for
conjugate, roving eye movements with full ductions. A moderate
angle esotropia of 30 PD was noted. Pupillary examination was
History and Exam normal, without evidence of a relative afferent pupillary defect.
A 2-month-old baby girl presented to the neuro-ophthalmology Anterior segment examination was normal in each eye. A dilated
clinic for unusual eye movements and poor visual behavior. The fundus examination revealed bilateral abnormalities involving
parents have noted that she does not look at her mother while the optic nerves. Foveae were normal.
nursing.

Birth history Clinical Course and Outcome

She was born full term at 38 weeks to a 16-year-old G2P0 In the setting of bilateral optic nerve hypoplasia, neuroimag-
mother. The pregnancy was uncomplicated. ing and a complete endocrinologic workup were pursued. MRI
revealed absence of the septum pellucidum and thinning of the
Maternal medical history optic nerves more prominently involving the right optic nerve.
No known medical illnesses. Prenatal vitamins were used The pituitary appeared normal radiographically. A full endocri-
throughout the pregnancy. nologic evaluation was normal.
The infant began working with a teacher for visual impair-
Family history ment through Early Intervention, with gradual improvement of
Noncontributory. vision. Patching of the dominant left eye was initiated to facili-
tate visual development in the right eye. She was followed at reg-
Social history ular intervals to monitor visual development. At the most recent
Mother and father are from El Salvador and currently reside in follow-up at age 4, visual acuity is 20/300 right eye and 20/200
the United States. There is no history of consanguinity. left eye. Strabismus surgery was performed to improve the ocular
alignment, with a marked improvement of her esotropia. She has
been registered with the appropriate social services for children
with legal blindness.
8 Advocating for Patients 2015 Subspecialty Day  |  Neuro-Ophthalmology

2015 Advocating for Patients

Lynn K Gordon MD PhD

Ophthalmology’s goal in protecting quality patient eye care aptly focused on these leaders’ concerns with its headline “Qual-
remains a key priority for the Academy. All ophthalmologists ity surgical eye care ensured through training.” CAEPS has ben-
should consider their contributions to the following three funds efitted from contributions to the SSF, having received significant
as (a) part of their costs of doing business and (b) their individual support from the fund.
responsibility in advocating for patients and their profession: Other state ophthalmology societies have also benefitted from
SSF distributions in 2015 and were able to successfully imple-
• Surgical Scope Fund (SSF)
ment patient safety advocacy campaigns to defeat attempts by
• OPHTHPAC® Fund
optometry to expand its scope of practice to include surgery. The
• State Eye PAC
Texas Ophthalmological Association was successful in its patient
Your ophthalmologist colleagues serving on Academy com- advocacy and public education efforts to defeat three different
mittees—the Surgical Scope Fund Committee, the Secretariat for optometric-backed surgical scope expansion bills in the Texas
State Affairs, and the OPHTHPAC Committee—are committing state legislature.
many hours on your behalf. The Secretariat for State Affairs is In addition, the Academy supported the Alaska Society of Eye
collaborating closely with state ophthalmology society leaders Physicians and Surgeons in opposing optometric surgery scope
to protect Surgery by Surgeons at the state level. Meanwhile, the legislation that posed a threat to patient surgical care. If enacted,
OPHTHPAC Committee is hard at work identifying congressio- the optometric surgery bill would have authorized optometrists
nal advocates in each state to maintain close relationships with in Alaska to perform surgery with lasers, scalpels, and needles,
federal legislators in order to advance ophthalmology and patient and to perform other surgical procedures. The legislation would
causes. Both groups’ ultimate goals are to ensure robust funds also have allowed optometrists to perform all injections except
for both the SSF and the OPHTHPAC Fund so that they are able intravitreal and to prescribe any controlled substances. Thanks
to (a) protect quality patient eye care, (b) protect ophthalmology to an effective Surgery by Surgeons advocacy campaign, with
practices from payment cuts, (c) reduce burdensome regulations, support from the SSF, this legislation died in committee. The
and (d) advance the profession by promoting funding for vision Alaska state legislature adjourned for the year on April 27.
research and expanded inclusion of ophthalmology in public and The Academy relies not only on the financial contributions
private programs. to the SSF from individual ophthalmologists and their business
These committed ophthalmologists serving on your behalf practices, but also on the contributions made by ophthalmic
have a simple message to convey: state, subspecialty, and specialized interest societies. Several
“We also need you”! subspecialty societies contributed to the Surgical Scope Fund in
2014, and the Academy counts on their contributions in 2015.
• We need you to contribute to each of these three funds.
• We need you to establish relationships with state and fed-
eral legislators. OPHTHPAC® Fund
• We need you to help us protect quality patient eye care
OPHTHPAC is a crucial part of the Academy’s strategy to
and the profession.
protect and advance ophthalmology’s interests in key areas
including physician payments from Medicare as well as pro-
Surgical Scope Fund tecting ophthalmology from federal scope of practice threats.
Established in 1985, OPHTHPAC is one of the oldest, largest,
The Surgical Scope Fund (SSF) provides grants to state ophthal-
and most successful political action committees in the physician
mology societies to support their legislative, regulatory, and
community and is very successful in representing your profes-
public education efforts to derail optometric surgery proposals
sion to the U.S. Congress. As one election cycle ends, a new one
that pose a threat to patient safety, quality of surgical care, and
starts. OPHTHPAC is always under financial pressure to support
surgical standards. Since its inception, the Surgery by Surgeons
our incumbent friends as well as to make new friends with can-
campaign—in partnership with state ophthalmology societies
didates. These relationships allow us to have a seat at the table
and with support from the SSF—has helped 32 state/territorial
and legislators willing to work on issues important to us and our
ophthalmology societies reject optometric surgery proposals.
patients. Among the significant achievements of OPHTHPAC
As of July 1, 2015, the Secretariat for State Affairs, in col-
are the following:
laboration with the California Academy of Eye Physicians and
Surgeons (CAEPS) and the California Medical Society, continues • Repealed the flawed Sustainable Growth Rate (SGR) for-
to battle an onerous optometric surgery scope of practice bill mula
(SB 622) in the Golden State. The Secretariat has reached out • Blocked the unbundling of the Medicare global surgery fee
to all ophthalmology subspecialty society partners to help in period
this effort, and several have stepped up to the plate. In addition, • Removed a provision in fraud and abuse legislation that
ophthalmology leaders at California academic institutions have targeted eyelid surgery
played a critical role by voicing their concerns about the Cali- • Protected your ability to perform in-office ancillary ser-
fornia surgery bill and the impact it would have on quality eye vices
care for patients. A June 24 op-ed in the San Francisco Examiner
2015 Subspecialty Day  |  Neuro-Ophthalmology Advocating for Patients 9

Surgical Scope Fund OPHTHPAC® Fund State Eye PAC

To derail optometric surgical scope of practice Ophthalmology’s interests at the federal level Support for candidates for State House and
initiatives that threaten patient eye safety and Senate
Support for candidates for U.S. Congress
quality of surgical care

Political grassroots activities, lobbyists and Campaign contributions, legislative education Campaign contributions, legislative education
media
No funds may be used for candidates or PACs.
Contributions: Unlimited Contributions: Limited to $5,000 Contribution limits vary based on state regula-
tions.
Individual, practice, and organization
Contributions are 100% confidential. Contributions above $200 are on the public Contributions are on the public record depend-
record. ing upon state statutes.

• Working to reduce the burdens from Medicare’s exist- Please respond to your Academy colleagues who are volun-
ing quality improvement programs such as the Electronic teering their time on your behalf to serve on the OPHTHPAC*
Health Record Meaningful Use program and Surgical Scope Fund** Committees, as well as your state
• Working in collaboration with subspecialty societies to ophthalmology society leaders, when they call on you and your
preserve access to compounded and repackaged drugs subspecialty society to contribute. Advocate for your patients
such as bevacizumab now!
Leaders of the North American Neuro-Ophthalmology Soci-
ety (NANOS) are part of the American Academy of Ophthalmol- *OPHTHPAC Committee
ogy’s Ophthalmic Advocacy Leadership Group (OALG), which
Donald J Cinotti MD (NJ) – Chair
has met every January for the past eight years in the Washington
Janet A Betchkal MD (FL)
D.C. area to provide critical input and to discuss and collaborate
William S Clifford MD (KS)
on the Academy’s advocacy agenda. The topics discussed at
Robert A Copeland Jr MD (Washington DC)
the 2015 OALG meeting included collaborative efforts on the
Anna Luisa Di Lorenzo MD (MI)
IRIS Registry and quality reporting under Medicare. As a 2015
Sidney K Gicheru MD (TX)
Congressional Advocacy Day (CAD) partner, NANOS ensured
Michael L Gilbert MD (WA)
a strong presence of neuro-ophthalmology specialists to support
Gary S Hirshfield MD (NY)
ophthalmology’s priorities as nearly 400 Eye M.D.s had sched-
Jeff S Maltzman MD (AZ)
uled CAD visits to members of Congress in conjunction with
Thomas J McPhee MD (AZ)
the Academy’s 2015 Mid-Year Forum in Washington. NANOS
Lisa Nijm MD JD (IL)
remains a crucial partner with the Academy in its ongoing fed-
Andrew J Packer MD (CT)
eral and state advocacy initiatives.
Diana R Shiba MD (CA)
Woodford S Van Meter MD (KY)
State Eye PAC John (“Jack”) A Wells III MD (SC)
It is also important for all ophthalmologists to support our Ex Officio Members
respective State Eye PACs because state ophthalmology societ-
Daniel J Briceland MD (AZ)
ies cannot count on the Academy’s SSF alone. The presence of a
Michael X Repka MD (MD)
strong State Eye PAC providing financial support for campaign
Russell Van Gelder MD PhD (WA)
contributions and legislative education to elect ophthalmology-
George A Williams MD (MI)
friendly candidates to the state legislature is also critical. The
Secretariat for State Affairs strategizes with state ophthalmology
societies on target goals for State Eye PAC levels. **Surgical Scope Fund Committee
Thomas A Graul MD (NE) – Chair
ACTION REQUESTED: ADVOCATE FOR YOUR Arezo Amirikia MD (MI)
PATIENTS!! Matthew F Appenzeller MD (NC)
Ronald A Braswell MD (MS)
Academy Surgical Scope Fund contributions are used to support
John P Holds MD (MO)
the infrastructure necessary in state legislative / regulatory battles
Cecily A Lesko MD FACS (NJ)
and for public education. PAC contributions are necessary at
William (“Chip”) W Richardson II MD (KY)
the state and federal level to help elect officials who will support
David E Vollman MD MBA (MO)
the interests of our patients. Contributions to each of these three
funds are necessary and should be considered the costs of doing Ex Officio Members
business. SSF contributions are completely confidential and may
Daniel J Briceland MD (AZ)
be made with corporate checks or credit cards, unlike PAC con-
Kurt F Heitman MD (SC)
tributions, which must be made by individuals and are subject to
reporting requirements.
10 Section II: Eye Pain and Headache 2015 Subspecialty Day  |  Neuro-Ophthalmology

Section II: Your “What” Hurts? Eye Pain and

Headache Made Ridiculously Simple

“Worst Headache of My Life!” “My head hurts for days on end…”

S Tonya Stefko MD John H Pula MD

C ase C ase

History and Exam History and Exam

A 44-year-old real estate professional noticed that his glasses did A 37-year-old man with no significant past medical history pres-
not seem to be working well for his left eye. Everything up and ents with a chief complaint of “My head hurts for days on end.”
to the left was blurred and lighter in color, he complained, for The headache was strictly left-sided with a retrobulbar compo-
about a month. He visited the optometrist, where his refraction nent. For the last 5 days, multiple headaches have occurred at the
had not changed. He was seen later that week by a retina special- same times of day, each one lasting ~70 minutes, the first always
ist, who noted 20/32 vision with correction O.U. and an other- waking him up at 4:30 a.m. With his headaches, the patient gets
wise entirely normal exam. Two weeks later, he had a visual field conjunctival injection and lacrimation of the affected side. When
test that showed a temporal and superior defect in the left eye, drinking alcohol or smoking a cigarette, the headache is exac-
with nonspecific change in the right. He was referred to neuro- erbated. The headaches are so severe that he is unable to sit still
ophthalmology and given an appointment with a VEP, about 6 during one and paces the room, or even bangs his head against
weeks in the future. a wall to try and alleviate them. Evaluation reveals an anxious
MRI was ordered by the optometrist and was pending insur- man, with normal acuity and color vision, and normal slitlamp
ance review and approval. Over the next 2 weeks, the patient and fundus exams. Motility and alternate cover test are normal.
felt increasing tired and achy and attributed these symptoms to There is a 2-mm relative ptosis on the left. He has anisocoria,
stress. He also experienced a dull, daily headache with mild light with right pupil 8 mm in the dark and 2 mm in the light; left eye
sensitivity. The headache initially responded to over-the-counter 3 mm in dark, 1 mm in light, without afferent pupillary defect.
ibuprofen treatment. Two days prior to his scheduled MRI, he There is dilation lag of the left eye with no vermiform move-
experienced sudden, excruciating holocranial headache with ments of the pupil.
photophobia. He had never before had such a severe headache.
This occurred at work, and he was taken by his colleagues to the
Clinical Course and Outcome
local emergency department for evaluation.
Based on exam, it was felt that the patient’s anisocoria was due
to autonomic dysfunction at the affected pupil. Two drops of
Clinical Course and Outcome
1.0% apraclonidine were administered to each eye. After 45
MRI brain with contrast showed a pituitary mass with hemor- minutes, the right pupil remained unchanged, with constriction
rhage. He was admitted for emergent neurosurgical intervention. from 8 mm to 2 mm, but the left pupil size changed to 9 mm in
He was found to have central hypoadrenalism, hypothyroidism, the dark and 8 mm in the light. In addition, after apraclonidine,
and possible diabetes insipidus, and his prolactin was mildly the left eyelid palpebral fissure increased and was now 1 mm
elevated. He awoke from surgery with markedly improved visual more open than the right.
fields and 20/20 BCVA O.U., 11/11 Ishihara color plates, nor- At this point, further history was obtained, with the patient
mal extraocular movement, and small relative afferent pupillary denying any recent cervical neck manipulation, trauma, or neck
defect O.S. pain. Carotid imaging was urgently obtained nevertheless, but
was negative for arterial dissection or other abnormality. The
following day, 1% hydroxyamphetamine drops were instilled
into each eye, and there was minimal change in either pupil size
after 1 hour. MRI of the brain and orbits, MRI of the neck, and
CT scan of the chest were obtained, and all were unremarkable.
While getting his brain MRI, the patient developed a typical
severe headache and was taken to the emergency room. He was
given 10L of 100% oxygen for 20 minutes, and his headache
resolved. He was then put on a course of oral steroids and vera-
pamil, with sumatriptan as needed. Within 1 week, his head-
aches improved significantly, although there was no change in
the anisocoria or ptosis.
2015 Subspecialty Day  |  Neuro-Ophthalmology Section II: Eye Pain and Headache 11

“My eye just aches all the time.”

Rod Foroozan MD

C ase

History and Exam Clinical Course and Outcome

A 49-year-old woman noted episodic headaches on the right side Palpation over the right trochlear region revealed no tenderness.
for the past 3 months. She described the headache, which could Palpation over the occiput reproduced pain similar to her prior
involve the top of her head, as a stabbing pain lasting seconds symptoms that radiated to the top of her head on the right side.
and occasionally associated with a milder headache in between Topiramate was discontinued and trigeminal neuralgia was
these episodes. On occasion she noted the pain over the right eye considered. She started carbamazepine but had no relief of symp-
as well. She was in good health apart from the headaches. She toms after 3 weeks.
had a motor vehicle accident without head trauma 1 year before An injection of 0.5% bupivacaine in the region of the right
the onset of symptoms. greater occipital nerve, lateral and inferior to the external occipi-
Ophthalmic examination revealed UCVA 20/20 in each eye tal protuberance, was performed. She reported relief of pain
with normal slitlamp examination (including gonioscopy) and within minutes of the injection. The pain relief lasted 4 weeks
funduscopy. MRI of the brain and orbits with contrast and before a mild discomfort in the same distribution recurred. Two
magnetic resonance angiography of the head and neck without months later a second injection largely relieved the symptoms,
contrast showed no abnormalities. She was diagnosed with with some intermittent mild pain occurring once every few
migraine and started on topiramate. Four weeks later she noted weeks.
no improvement in the episodic pain.
12 Section II: Eye Pain and Headache 2015 Subspecialty Day  |  Neuro-Ophthalmology

Mini-Talk: Where Do I Begin? Headache History and

Exam Made Ridiculously Simple
Lynn K Gordon MD PhD

When patients present to the ophthalmologist with a chief com- motor cranial mononeuropathies are often initially associated
plaint of headache, there are often immediate concerns for the with pain or headache. Does the patient have a fever, rash, stiff
physician. Is the pain attributable to eye disease? Does the pain neck, or discomfort with eye movements in association with
arise from a headache syndrome? Is the symptom of pain evi- the headache? Any infectious or meningeal signs such as fever,
dence for some disease entity that could cause serious morbidity sweats, and/or neck pain worse with flexion must be promptly
or even mortality? After all, the eye and periocular structures evaluated.
have sensory innervation from the trigeminal nerve; therefore
pain in the head can arise from the eye, periorbita, or primary 4.  What is your past and current medical history? Specifically,
or secondary headache disorders. How can one quickly but is there a history of any cancer, autoimmune disease, or
thoroughly evaluate the patient and form a strategic plan, when immunosuppression (medication induced or HIV)? Is it possible
appropriate, for additional diagnostic testing or therapeutic that the patient is pregnant? Is there a history of seizures?
interventions? This presentation concentrates on simplifying the These would all be red flags that may require additional testing.
headache history and examination.
5.  Do you have associated symptoms of weight loss, fevers,
scalp pain, jaw or tongue claudication, and/or episodes of
History transient vision loss?
The goal of the history is to narrow the differential diagnosis and Always remember giant cell arteritis in the differential diagno-
determine whether and what additional testing is indicated. The sis of individuals over the age of 50 with new-onset headache.
following are the typical questions that you should ask when a Remember, if your suspicion is high for giant cell arteritis you
patient presents with a headache: must start high-dose steroids pending the full evaluation of the
patient.
1.  Do you have a history of headaches? If yes, then is this
headache similar to those you have had in the past? 6.  Are there any associated focal neurologic symptoms?
It is not typical for a patient to see their ophthalmologist during These would all be red flags in the history that would require
their first or worst headache of their life. However, there might additional testing.
be a circumstance when you would be consulted on this type of
patient in an emergency room. “First or worst” are red flags that 7.  What medications are you taking?
may require urgent evaluation. If the headache is similar to prior If the patient is using a migraine prophylactic agent such as topi-
headaches, without a change in frequency or severity, additional ramate, then failure to respond to the medicine may be the cause
questions will help to define the differential diagnosis. of the headache. Don’t forget, angle-closure glaucoma may occur
in such patients and be misdiagnosed as headache! Overuse of
2.  Is there a pattern to the headaches: are they associated with over-the-counter analgesics may be associated with medication
specific triggers or do they occur at a specific time or times overuse headache or rebound headache.
during the day? Is there a periodicity to the headaches? For
example, have you had weeks or months of regular headaches
in the past? Does the headache interfere with your usual Clinical Exam
activities? What is the location and character of the headache? The history has already helped you decide on the focus of the
Does eye movement aggravate the pain? examination. However there are still a few remaining details that
Migraine headaches are often associated with triggers that can will help in determining the next steps.
include menses, food, alcohol, stress, and fatigue. Cluster head- Diseases of the eye may cause pain that is interpreted by the
aches tend to occur recurrently at specific times of the day and patient as a headache. Common diseases that may have a sub-
may occur for one to many weeks followed by a headache-free acute presentation include ocular surface disease such as dry eye
interval. Eye movement often increases trochlear headache. or chronic exposure keratitis. Thyroid eye disease may present
with ocular or orbital discomfort. Severe, acute, intermittent, or
3.  Do you have any associated symptoms with the headache? chronic pain may result also from keratitis, intraocular inflam-
Specifically ask about nausea or vomiting, phonophobia, photo- mation, angle-closure glaucoma, and orbital inflammatory dis-
phobia, and/or worsening with activity. These are all symptoms eases.
associated with migraine. Cluster headaches often are associ- Perform a thorough ocular and orbital examination. Specifi-
ated with nasal congestion or rhinorrhea, unilateral ptosis or lid cally, examine the lids and orbit for signs of ptosis, proptosis,
edema, unilateral conjunctival injection, miosis, or facial sweat- displacement of the globe, or lid retraction. Remember to palpate
ing. In addition, patients often are restless during the headaches the trochlea to help identify cases of trochlear headache.
and prefer to keep moving, not still. The autonomic symptoms Identify the BCVA and perform color vision screening and
can also be seen with other classifications of the trigeminal auto- visual field testing. Examine the pupil carefully for anisocoria or
nomic cephalgias. Is there double vision? Microvascular ocular for a relative afferent pupillary defect. Perform a motility evalu-
2015 Subspecialty Day  |  Neuro-Ophthalmology Section II: Eye Pain and Headache 13

ation in order to detect subtle signs of cranial nerve involvement.

The slit lamp and dilated evaluation of the fundus will identify
any inflammatory or infectious involvement of the eye or ocular
adnexa and, if present, will identify papilledema.

Next Steps
The careful history and physical examination determine the next
steps. Patients with atypical symptoms, red flags in the history
or examination, and autonomic symptoms generally will require
neuroimaging. The choice of neuroimaging studies is dictated
by the clinical suspicion, the availability of testing modality, and
the expertise of the imaging facility. A noncontrast CT scan is
generally not recommended as an initial study for patients with
isolated headache. Laboratory evaluations may be required
when considering systemic inflammatory diseases. After neuro-
imaging studies are performed, evaluation of the cerebral spinal
fluid is required when papilledema is observed, when there are
new-onset seizures, or when suspicion exists for meningitis or
encephalitis.
14 Section II: Eye Pain and Headache 2015 Subspecialty Day  |  Neuro-Ophthalmology

“The light!! It hurts my eyes!!” Past medical history reveals controlled hypertension, benign
prostatic hyperplasia, and hypothyroidism. Of note, he attributes
Bradley J Katz MD his ptosis and facial asymmetry to childhood head injury sus-
tained when kicked in the head by a cow. Current medications
C ase include doxazosin, lisinopril, levothyroxine, and finasteride. He
has no known medication allergies. Social history and family his-
tory are unrevealing.
History and Exam On exam, Snellen visual acuity was 20/20 in each eye, with-
A 45-year-old female presented with a chief complaint of light out afferent pupillary defect (APD). Color perception by Ishi-
sensitivity. hara plates was 8/11 in the right eye and 11/11 in the left eye.
Her past medical history was unremarkable except for occa- On dilated ophthalmoscopy, the right disc margin was slightly
sional “sinus headaches.” She reported no drug allergies and blurred, with cup-to-disc of 0.2 in each eye with otherwise nor-
took no medications other than over-the-counter nonsteroidal mal fundi. External exam revealed 1-mm ptosis on the right and
anti-inflammatory drugs. Her symptoms had been present for the 2 mm of left ptosis, asymmetric facies, and a large scar on the left
past 9 months and she’d consulted with two other eye doctors, cheek. Ocular motility revealed decreased adduction of the right
who’d told her that her eyes were completely normal. Although eye and the alignment measurements below:
she’d been “light sensitive” for most of her life, her symptoms
were now to the point where she often wore sunglasses indoors.
6 XT
Her light sensitivity was beginning to interfere with her ability
to work at her occupation in data entry. Her boss had refused to 1 RHT
allow her to remove the fluorescent lights above her cubicle.
Her eye examination was entirely normal. 1 XT 2 XT 30 XT
<1 RHT 6 RHT 6 RHT
Clinical Course and Outcome
4 XT
Further questioning revealed that this patient had frequent
headaches and that these headaches were often unilateral with a 10 RHT
throbbing quality, increased light sensitivity, occasional sound
sensitivity (“phonophobia”) and occasional nausea. She reported
more than 15 headache days per month. This constellation of What is the most likely diagnosis?
symptoms is consistent with a diagnosis of chronic migraine. She
was using ibuprofen 800 mg once or twice a day, nearly every 1. Post-concussive headache with decompensated exophoria
day, indicating that she may also be suffering from rebound 2. Myasthenia gravis
headache. 3. Pupil-sparing aneurysmal third nerve palsy
She was prescribed FL-41 tinted spectacles for indoor use and 4. Temporal arteritis
was scheduled to see a neurologist for prophylactic and acute 5. Complicated migraine
treatment of migraine.
Clinical Course and Outcome
Given his ptosis, transient binocular diplopia, blurred vision, and
facial pain, the patient was admitted to the neurology service.
“It hurts when I talk, and this cough Neuroimaging including brain MRI and MRA revealed normal
won’t go away.” intracranial vasculature and mild, diffuse small vessel ischemic
changes attributable to age, and excluded stroke. Orbits were
Gabrielle R Bonhomme MD unremarkable. MRA of the neck excluded carotid dissection
or stenosis. Acetylcholine receptor antibody panel was sent to
CASE evaluate for myasthenia and was normal. ESR was 21, Hb was
11, and CRP was elevated at 1.674 mg/dL. Right temporal artery
biopsy was performed and was positive for temporal arteritis.
History and Exam The patient was treated with IV methylprednisolone during inpa-
An 82-year-old male farmer presents with 2 weeks of intrac- tient stay, with 1 mg/kg prednisone taper directed by rheumatol-
table dry cough, intermittent blurred vision in his right eye, and ogy. His cough, headaches, mouth pain, jaw claudication, and
transient, binocular, horizontal diplopia only on left gaze. He scalp tenderness quickly resolved on steroids.
also reports dull right neck, jaw, and mouth pain while eating or
yawning. Other than longstanding, asymmetric ptosis, he was in
his usual state of good health prior to symptom onset and denies
illness or upper respiratory infection. Prior to presenting to the
ER for worsening pain symptoms, he saw his dentist and was
told his exam was normal. He was evaluated by his primary care
provider with chest X-ray, which was negative.
2015 Subspecialty Day  |  Neuro-Ophthalmology Section III: Double Vision and Nystagmus 15

Section III: Double Vision and Nystagmus Made

Ridiculously Simple

“I see double, and my eyelid is in the “I see two golf club heads when I
way.” putt.”
Paul H Phillips MD Courtney E Francis MD

C ase C ase

History and Exam History and Exam

A 60-year-old man had binocular, horizontal, diplopia worse in A 57-year-old African American man presents to his ophthal-
right gaze that first occurred 1 week prior to presentation. He mologist with a complaint of progressively worsening diplopia
denied decreased vision and ocular pain. His past medical his- for the past 6 months. He reports that when he golfs, he gets
tory was remarkable for diabetes and hypertension. Medications double vision as he follows the ball in the air after he drives the
included insulin and lisinopril. He consulted his local eye doctor, ball. On exam, his acuity is 20/20 in both eyes. Slitlamp exam
who diagnosed him with an “ischemic cranial nerve palsy.” and funduscopic exam show mild cataracts but are otherwise
Ophthalmologic examination: Visual acuity was 20/20 O.U. unremarkable. He is noted to have a chin-up position. Exoph-
Confrontation visual fields were full O.U. External and slitlamp thalmometry reveals 1 mm of proptosis on the left side. Motility
examination were normal. Ocular motility examination showed exam shows a mild supraduction deficit in the left eye, otherwise
a complete abduction deficit O.D. Pupils were equal, reactive, full. On alternate cover testing, he has a 12 PD right hypertropia
without a relative afferent pupillary defect. Funduscopic exami- in primary gaze, increasing to 25 in upgaze and decreasing to 6
nation was normal, with a flat optic disc in both eyes. in downgaze. The deviation is fairly similar in right and left gazes
Further diagnostic testing and treatment? and right and left head tilts.

Clinical Course Clinical Course and Outcome

Two weeks after presentation, the patient complained of right In summary, this is a case of binocular vertical diplopia with
upper lid ptosis and anisocoria. Physical examination showed evidence of limited supraduction in one eye with associated
the previous complete right abduction deficit as well as right mild proptosis. The differential diagnosis for this case includes
upper lid ptosis and mild limitations of adduction, elevation, mechanical and paretic causes of limited extraocular movements.
and depression. Pupil examination showed anisocoria with a A detailed history and review of systems is important to narrow
3-mm pupil O.D. and a 4-mm pupil O.S. with no relative affer- down potential etiologies. The patient should be asked about a
ent pupillary defect. There was a right pupil dilation lag, and the history of thyroid dysfunction, prior head or facial trauma, and
amount of anisocoria increased with dim illumination. prior eye surgery (particularly retinal detachment repair, scleral
A diagnostic test was performed. buckle placement, or previous retrobulbar block). A history of
The pupil examination showed Horner syndrome O.D. The prior malignancy is also important to note.
combination of CN VI palsy, CN III palsy, and a Horner syn- Congenital or traumatic fourth nerve palsies are the most
drome O.D. localized the pathology to the right cavernous sinus common cause of acquired vertical deviations. Patients typically
and mandated neuroimaging. present with a hyperdeviation that worsens in the contralateral
An MRI of the brain with gadolinium showed a right cavern- gaze and ipsilateral head tilt; however, longstanding deviations
ous sinus mass consistent with a meningioma. may show some spread of comitance. Symptoms are typically
The patient did not elect to pursue further treatment. worst in activities requiring downgaze, such as reading or walk-
ing downstairs. On exam, a contralateral head tilt is often pres-
ent, with fairly full extraocular movements and varying amounts
of ipsilateral inferior oblique overaction. Vertical fusional ampli-
tudes are often higher than normal with congenital palsies.
Thyroid eye disease (TED) is another frequent cause of
vertical diplopia, as the inferior rectus muscle is the most com-
monly involved muscle, followed by the medial and superior
rectus muscles. Enlargement of the muscle leads to a restrictive
strabismus and a hypotropia on the affected side. Patients have
decreased symptoms in downgaze and so may adopt a chin-up
position in order to reduce symptoms of diplopia (as opposed to
the head tilt frequently seen in fourth nerve palsies). TED most
commonly occurs in the setting of Graves disease, but patients
may also present with a history of hypothyroidism or no prior
16 Section III: Double Vision and Nystagmus 2015 Subspecialty Day  |  Neuro-Ophthalmology

thyroid dysfunction. Other findings consistent with TED can Her medical history was significant for ovarian cancer that
be helpful in confirming the diagnosis, which is typically a clini- had been diagnosed and treated 3 years prior. She was status-
cal one. Lid retraction, lid lag, temporal flare, lagophthalmos, post hysterectomy, bilateral salpingo-oopherectomy, and che-
limited abduction and resultant esotropia (due to medial rectus motherapy with cisplatin and etoposide. Post-treatment, she
restriction), and proptosis can all be seen in TED, with lid lag developed gait difficulty with sensory loss in her feet that was
being particularly specific. Elevation in IOP in upgaze and posi- attributed to chemotherapy-induced peripheral neuropathy.
tive forced ductions can be signs of a restrictive strabismus, but On exam, acuity was 20/30 O.U. Color vision, pupils, visual
are not specific for TED. For patients without a clear history of fields, and fundus were normal. Eye movement range was full.
hyperthyroidism or lack of other findings on exam, orbital imag- Vertical oscillations were seen in primary gaze that increased in
ing can be helpful in ruling out other causes, including orbital lateral and downgaze and decreased in upgaze. It was character-
masses and inflammatory diseases such as orbital myositis. A ized as a slow drift upward with a fast corrective jerk movement
noncontrast orbital CT shows enlargement of the affected mus- downwards.
cles, with sparing of the muscle tendons, with rare involvement What would be the next step?
of the lateral rectus muscle. Patients presenting with an exotropia
and a diagnosis of TED should be evaluated for possible concur-
Clinical Course and Outcome
rent ocular myasthenia gravis, due to the increased association of
the two diseases. The vertical oscillations seen on examination represented
downbeat nystagmus (DBN). The immediate consideration in
this patient would be to determine if there is any relationship
Selected Readings
between the nystagmus and her ovarian cancer history. The
1. Harrad R. Management of strabismus in thyroid eye disease. Eye cancer history was several years ago, and she was closely fol-
2015; 29:234-237. lowed by her gynecologic oncologist, who reported the patient’s
2. Peragallo JH, Velez FG, Demer JL, Pineles SL. Postoperative drift in cancer to be in remission. Brain metastasis from ovarian cancer is
patients with thyroid ophthalmopathy undergoing unilateral infe- uncommon but must be considered. Thus, brain MRI with con-
rior rectus muscle recession. Strabismus. 2013; 21(1):23-28. trast would be the most appropriate initial diagnostic test. Other
structural lesions that might be found on brain MRI and should
3. Volpe NJ, Mirza-George N, Binenbaum G. Surgical management of
vertical ocular misalignment in thyroid eye disease using an adjust-
also be in the differential diagnosis in a young woman with new-
able suture technique. J AAPOS. 2012; 16(6):518-522. onset DBN include a Chiari I malformation (a common cause of
DBN), leptomeningeal enhancement (suggesting carcinoma or
4. Bothun ED, Scheurer RA, Harrison AR, Lee MS. Update on thyroid infection in the cerebrospinal fluid), and cerebellar or medullary
eye disease and management. Clin Ophthalmol. 2009; 3:543-551.
demyelination or stroke.
5. Chen VM, Dagi LR. Ocular misalignment in Graves disease may Brain MRI with contrast was normal.
mimic that of superior oblique palsy. J Neuroophthalmol. 2008; Patient was also sent by the ophthalmologist for a neurologic
28(4):302-304. consultation for her walking difficulties. In addition to the DBN,
the neurologist reported two other findings: (1) poor sensation
in her feet with reduced ankle reflexes attributed to her known
chemotherapy-induced neuropathy and (2) a wide-based gait
suggestive of ataxia attributed to a cerebellar problem.
“Things are blurry and jumpy when I Given the lack of an answer for a cerebellar process with
read.” DBN and ataxia, paraneoplastic cerebellar degeneration was
Janet C Rucker MD highly suspect. Though isolated idiopathic DBN is quite com-
mon, the presence of ataxia and her history of ovarian cancer
C ase were quite concerning for a link between her exam findings and
her cancer history.
Lumbar puncture revealed normal cerebrospinal fluid, includ-
History and Exam ing negative cytology. Chest, abdomen, and pelvic CT scans were
normal. Anti-GAD antibodies were negative, and thiamine level
A 29-year-old woman presented to her ophthalmologist report- was normal. A paraneoplastic panel revealed anti-Yo antibod-
ing difficulty reading due to blurry vision. She explained that ies in the serum. She was treated with a course of IVIg. Pelvic
words seemed to “jump up and down” when she tried to read a PET CT scan revealed lymph node enlargement suggestive of
book. She had first noticed this several months earlier. She occa- recurrent cancer. CT-guided biopsy confirmed recurrent ovarian
sionally noticed the jumping while watching television, but it was cancer.
more bothersome with reading. She also reported that she felt
less steady while walking than usual. She otherwise felt well and
had no other new visual or neurologic symptoms. She specifically
denied headaches or double vision.
2015 Subspecialty Day  |  Neuro-Ophthalmology Section III: Double Vision and Nystagmus 17

Mini-Talk: Orbital Pulleys and Muscles Made

Ridiculously Simple
Joseph L Demer MD PhD

This mini-talk attempts humor in a valiant but probably futile determined by the relationship between its pulley
effort to convince neuro-ophthalmologists that they should and its scleral insertion.
care about other things in the orbit besides nerves. All other
E. Peer pressure: Normal people have stereotypic pul-
approaches have so far failed, anyway.
ley locations. But not everyone conforms.
FDA Disclosure: Surface coils not approved by FDA were F. Orbital layers of the oblique EOMs translate the
employed for some imaging studies. rectus pulleys in the coronal plane.
1. The orbital layer of the inferior oblique inserts
Grant Support: USPHS National Eye Institute EY08313, and
on the inferior rectus and lateral rectus pulleys.
Research to Prevent Blindness. No financial conflict of interest
exists. 2. The orbital layer of the superior oblique inserts
on the superior oblique sheath posterior to the
trochlea; the sheath travels through the trochlea
I. “I am shocked! Shocked!” Many of our 19th-century
and inserts on the superior rectus pulley.
beliefs about the extraocular muscles (EOMs) are
incorrect! 3. In convergence, rectus pulley array excyclo
rotates, due to orbital layers of oblique EOMs.
A. EOMs are homogeneous structures that rotate the
globe. G. Coordinated movements of the pulley’s ocular rota-
tions account for Listing’s law of torsion and previ-
D. EOMs follow straight paths from orbital apex to
ously mysterious aspects of ocular kinematics.
scleral insertion.
H. Pulley composition and structure are highly stereo-
C. Everyone has the same arrangement of EOMs.
typic. Pulleys are composed of dense, woven col-
D. Abnormalities of EOMs are limited to underaction lagen, stiffened by elastin and incorporating smooth
(paralysis or paresis), overaction, innervational muscles having autonomic innervation.
miswiring, or stiffness.
I. Pulleys reconfigure in situations not conforming to
E. All important pathophysiology of EOMs can be Listing’s law of ocular torsion.
diagnosed by clinical motility examination.
1. Rectus pulley shirts torsionally with the eye dur-
F. Orbital connective tissues and EOM sleeves are not ing ocular torsion evoked by head tilting.
clinically very important.
2. Rectus pulley array extorts during convergence,
II. Amazing Revelations From 21st-Century Science required for stereopsis.
A. Surface coil MRI of living human orbits has near IV. Duplicity of EOMs: Different Parts Do Different
microscopic resolution. Things
B. Digital imaging of immuno- and histo-chemically A. Orbital layer
stained whole human orbits permits 3-D reconstruc-
1. Contains 40%-50% of total muscle fibers
tion and correlation with in vivo MRI.
2. Inserts on the connective tissue pulley, not on the
C. Classical physiologic data was equivocal and can be
globe
more satisfactorily reinterpreted in light of recent
anatomical findings. 3. Translates the pulley along EOM axis
III. Foolish EOMs don’t know their names. They just pull 4. Does not rotate the globe
along paths defined by connective tissue pulleys.
B. Global layer
A. Rectus EOMs do not follow shortest, straight-line
1. Contains 50%-60% of total muscle fibers
paths from orbital apex to scleral insertion.
2. Contiguous with the insertional tendon
B. Connective tissue rings called pulleys are located
between the globe equator and posterior pole that 3. Rotates the globe
constrain EOM paths.
C. Global layer compartments
C. Pulleys serve as the functional mechanical origins of
1. Separately controllable neuromuscular units
the EOMs.
2. Apply force to different scleral insertion points
D. Any rectus EOM can have horizontal, vertical, and
along broad EOM tendons
torsional actions. Pulling direction of any EOM is
18 Section III: Double Vision and Nystagmus 2015 Subspecialty Day  |  Neuro-Ophthalmology

3. Differential function in inferior rectus, lateral VI. Nothing can protect pulleys from surgical exploitation
rectus, medial rectus, and superior oblique (verti- by ophthalmologists who are in the know.
cal vs. torsional)
A. Conventional strabismus surgical approaches
V. Rebels With a Strabismus Cause expose the anterior parts of the pulleys.
Heterotopy (malpositioning) of rectus pulleys causes B. Suggestion: Handle pulley tissues conservatively,
incomitant strabismus. unless aim is to alter pulleys.
A. Bad pulleys masquerade as cranial nerve palsies. A C. Lost muscles retract into their pulleys, where they
pulley out of place will cause rectus EOMs to pull in can generally be found.
an oblique or torsional direction.
D. Efficacious pulley surgeries have been studied by
B. Heterotopic pulleys can be diagnosed by appropri- MRI.
ate orbital MRI or CT.
1. Retroequatorial myopexy: Mechanism shown
C. Some pulleys are born for trouble. by MRI; interference of myopexy suture with the
pulley. Stretching of the pulley suspension creates
1. Congenital A pattern pulley heterotopy
a mechanical restriction in the field of action of
a. Superior location of lateral relative to medial the operated EOM.
rectus pulley in one or both orbits, so that the
2. Augmented rectus transposition (Foster)
medial acts as a relative depression in adduc-
tion a. More effective than full tendon width rectus
transfer for paralytic strabismus
b. Or lateral location of inferior relative to supe-
rior rectus pulley in one or both orbits, so b. Produces large shifts in pulley position into
that the inferior rectus acts as an abductor in the direction of the paralyzed EOM
depression
c. Benefits from extensive pulley dissection
c. Both kinds of heterotopy will manifest over-
E. Posterior fixation (“fadenoperation”) works by
depression in adduction and be confused
creating hindrance to posterior pulley shift during
clinically with “superior oblique overaction”
EOM contraction.
2. Congenital V pattern pulley heterotopy
1. No scleral suturing is required. Just sew the pul-
a. Inferior location of lateral relative to medial ley to the muscle belly.
rectus pulley in one or both orbits, so that
2. Modified approach works as well as conven-
the medial rectus acts as a relative elevator in
tional fadenoperation for acquired esotropia
adduction
with high accommodative convergence-to-
b. Or medial location of inferior relative to accommodation ratio.
superior rectus pulley in one or both orbits, so
3. Modified approach avoids risk of scleral perfora-
that the inferior rectus acts as an adductor in
tion.
depression
F. Conventional surgery works in sagging eye syn-
c. Both kinds of heterotopy will manifest over-
drome.
elevation in adduction and be confused clini-
cally with “inferior oblique overaction” 1. “All-in” medial rectus recession works well for
ARDE.
D. Some pulleys have trouble thrust upon them.
Hint: Do not be timid. Recess both medial rectus
1. Sagging eye syndrome: Failure of the LR-SR
muscle in nearly every patient, and recess for a
band ligament may cause 15%-20% of adult
target angle twice the largest ET measured in
acquired strabismus in U.S. practices.
any distance gaze position. Check convergence
a. Age-related distance esotropia (ARDE): Bilat- amplitudes first, consider topical anesthesia.
erally symmetrical failure causes symmetrical
2. Partial rectus tenotomy under topical anesthesia
lateral rectus sag, converting some lateral rec-
works well for cyclovertical strabismus.
tus force from abduction to infraduction.
b. Asymmetrical lateral rectus sag causes
Selected Readings (Hidden in Plain Sight All This
hypotropia and excyclotropia ipsilateral to
Time!)
the greater sag. This may resemble superior
oblique palsy, except that excyclotropia is in 1. Demer JL, Miller JM, Poukens V, Vinters HV, Glasgow B. Evidence
the lower eye. for fibromuscular pulleys of the recti extraocular muscles. Invest
Ophthalmol Vis Sci. 1995; 36:1125-1136.
2. Heavy eye syndrome: Large angle esotropia and
ipsilateral hypotropia associated with high axial 2. Porter JD, Poukens V, Baker RS, Demer JL. Structure-function
correlations in the human medial rectus extraocular muscle pulley.
myopia. The lateral rectus pulley slips under
Invest Ophthalmol Vis Sci. 1996; 37:468-472.
the globe, converting the lateral rectus from an
abductor to a depressor.
2015 Subspecialty Day  |  Neuro-Ophthalmology Section III: Double Vision and Nystagmus 19

3. Clark RA, Miller JM, Demer JL. Location and stability of rectus 22. Demer JL, Kono R, Wright W. Magnetic resonance imaging of
muscle pulleys: muscle paths as a function of gaze. Invest Ophthal- human extraocular muscles in convergence. J Neurophysiol .2003;
mol Vis Sci. 1997; 38:227-240. 89:2072-2085.
4. Demer JL, Poukens V, Miller JM, Micevych P. Innervation of extra- 23. Demer JL, Oh SY, Clark RA, Poukens V. Evidence for a pulley
ocular pulley smooth muscle in monkey and human. Invest Oph- of the inferior oblique muscle. Invest Ophthalmol Vis Sci. 2003;
thalmol Vis Sci. 1997; 38:1774-1785. 44:3856-3865.
5. Clark RA, Miller JM, Rosenbaum AL, Demer JL. Heterotopic rec- 24. Demer JL. Ocular kinematics, vergence, and orbital mechanics.
tus muscle pulleys or oblique muscle dysfunction? J AAPOS. 1998; Strabismus 2003; 11:49-57.
2:17-25.
25. Demer JL. Pivotal role of orbital connective tissues in binocular
6. Demer JL, Clark RA, Miller JM. Role of orbital connective tissue in alignment and strabismus. The Friedenwald Lecture. Invest Oph-
the pathogenesis of strabismus. Am Orthoptic J. 1998; 48:56-64. thalmol Vis Sci. 2004; 45:729-738.
7. Clark RA, Isenberg SJ, Rosenbaum AL, Demer JL. Posterior fixa- 26. Clark RA, Ariyasu R, Demer JL. Medial rectus pulley posterior
tion sutures: a revised mechanical explanation for the fadenopera- fixation is as effective as scleral posterior fixation for acquired eso-
tion based on rectus extraocular muscle pulleys. Am J Ophthalmol. tropia with a high AC/A ratio. Am J Ophthalmol. 2004; 137:1026-
1999; 128:702-714. 1033.
8. Demer JL, Miller JM. Orbital imaging in strabismus surgery. In: 27. Pirouzian A, Goldberg RA, Demer JL. Inferior rectus pulley hin-
Rosenbaum AL and Santiago P., eds. Advanced Strabismus Surgery. drance: orbital imaging mechanism of restrictive hypertropia fol-
New York: Mosby; 1999:84-98. lowing lower lid surgery. J AAPOS. 2004; 8:338-344.
9. Demer JL, Clark RA, Miller JM. Heterotopy of extraocular muscle 28. Clark RA, Ariyasu R, Demer JL. Medial rectus pulley posterior
pulleys causes incomitant strabismus. In: Lennerstrand G, ed. fixation: a novel technique to augment recession. J AAPOS. 2004;
Advances in Strabismology. Amsterdam: Swets; 1999: 91-94. 8:451-456.
10. Demer JL, Oh SY, Poukens V. Evidence for active control of rec- 29. Kono R, Poukens V, Demer JL. Superior oblique muscle layers in
tus extraocular muscle pulleys. Invest Ophthalmol Vis Sci. 2000; monkeys and humans. Invest Ophthalmol Vis Sci. 2004; 46:2790-
41(6):1280-1290. 2799.
11. Demer JL. Extraocular muscles. In: Jaeger EA and Tasman PR., eds. 30. Demer JL, Clark RA. Magnetic resonance imaging of human extra-
Clinical Ophthalmology. Philadelphia: Lippincott Williams and ocular muscles during static ocular counter-rolling. J Neurophysiol.
Wilkins; 2000, vol. 1, ch. 1. 2005; 94:3292-3302.
12. Clark RA, Miller JM, Demer JL. Three-dimensional location of 31. Demer JL. Current concepts of mechanical and neural factors in
human rectus pulleys by path inflections in secondary gaze posi- ocular motility. Curr Opin Neurol. 2006; 19:4-13.
tions. Invest Ophthalmol Vis Sci. 2000; 41:3787-3797.
32. Demer JL. Gilles Lecture: Ocular motility in a time of paradigm
13. Oh SY, Poukens V, Demer JL. Quantitative analysis of extraocular shift. Clin Experiment Ophthalmol. 2006; 34:822-826.
muscle layers in monkey and human. Invest Ophthalmol Vis Sci.
33. Demer JL. Mechanics of the orbita. Dev Ophthalmol. 2007;
2001; 42:10-16.
40:132-157.
14. Clark RA, Demer JL. Rectus extraocular muscle pulley displace-
34. Lim KH, Poukens V, Demer JL. Fascicular specialization in human
ment after surgical transposition and posterior fixation for treat-
and monkey rectus muscles: evidence for structural independence
ment of paralytic strabismus. Am J Ophthalmol. 2002; 133:119-
of global and orbital layers. Invest Ophthalmol Vis Sci. 2007;
128.
48:3089-3097.
15. Demer JL. The orbital pulley system: a revolution in concepts of
35. Kono R, Okanobu H, Ohtsuki H, Demer JL. Displacement of the
orbital anatomy. Ann NY Acad Sci. 2002; 956:17-32.
rectus muscle pulleys simulating superior oblique palsy. Japn J
16. Oh SY, Clark RA, Velez F, Rosenbaum AL, Demer JL. Incomitant Ophthalmol. 2008; 52:36-43.
strabismus associated with instability of rectus pulleys. Invest Oph-
36. Demer JL. Inflection in inactive lateral rectus muscle: evidence sug-
thalmol Vis Sci. 2002; 43:2169-2178.
gesting focal mechanical effects of connective tissues. Invest Oph-
17. Kono R, Clark RA, Demer JL. Active pulleys: magnetic resonance thalmol Vis Sci. 2008; 49:4858-4864.
imaging of rectus muscle paths in tertiary gazes. Invest Ophthalmol
37. Demer JL, Clark RA, Crane BT, Tian JR, Narasimhan A, Karim
Vis Sci. 2002; 43:2179-2188.
S. Functional anatomy of the extraocular muscles during vergence.
18. Kono R, Poukens V, Demer JL. Quantitative analysis of the struc- Prog Brain Res. 2008; 171:21-28.
ture of the human extraocular muscle pulley system. Invest Oph-
38. Clark RA, Demer JL. Posterior inflection of weakened lateral rectus
thalmol Vis Sci. 2002; 43:2923-2932.
path: connective tissue factors reduce response to lateral rectus
19. Clark RA, Demer JL. Effect of aging on human rectus extraocular recession. Am J Ophthalmol. 2009; 147:127-133.
muscle paths demonstrated by magnetic resonance imaging. Am J
39. Rutar T, Demer JL. “Heavy eye syndrome” in the absence of high
Ophthalmol. 2002; 134:872-878.
myopia: a connective tissue degeneration in elderly strabismic
20. Demer JL. A 12 year, prospective study of extraocular muscle imag- patients. J AAPOS. 2009; 13:36-44.
ing in complex strabismus. J AAPOS. 2003; 6: 337-47.
40. da Silva Costa RM, Kung J, Poukens V, Yoo L, Tychsen L, Demer
21. Miller JM, Demer JL, Poukens V, Pavlowski DS, Nguyen HN, JL. Intramuscular innervation of primate extraocular muscles:
Rossi EA. Extraocular connective tissue architecture. J Vision. unique compartmentalization in horizontal recti. Invest Ophthal-
2003; 2:12-23. mol Vis Sci. 2011; 52:2830-2836.
41. Demer JL, Dusyanth A. T2 fast spin echo magnetic resonance imag-
ing of extraocular muscles. J AAPOS. 2011; 15:17-23.
20 Section III: Double Vision and Nystagmus 2015 Subspecialty Day  |  Neuro-Ophthalmology

42. Demer JL, Clark RA, Kung J. Functional imaging of human extra- 49. Clark RA, Demer JL. Differential lateral rectus compartmental con-
ocular muscles in head tilt dependent hypertropia. Invest Ophthal- traction during ocular counter-rolling. Invest Ophthalmol Vis Sci.
mol Vis Sci. 2011; 52:3023-3031. 2012; 53:2887-2896.
43. Demer JL, Clark RA, da Silva Costa RM, Clark RA, Kung J, Yoo 50. Chaudhuri Z, Demer JL. Sagging eye syndrome: connective tis-
L. Expanding repertoire in the oculomotor periphery: selective com- sue involution causes horizontal and vertical strabismus in older
partmental function in rectus extraocular muscles. Ann NY Acad patients. JAMA Ophthalmol. 2013; 131:619-625.
Sci. 2011; 1233:8-16.
51. Demer JL, Clark RA. Differential compartmental function of
44. Wabulembo G, Demer JL. Long term outcome of medial rectus medial rectus muscle during conjugate and converged ocular adduc-
recession and pulley posterior fixation in esotropia with high AC/A tion. J Neurophysiol. 2014; 112(4):845-855.
ratio. Strabismus 2012; 20:115-120.
52. Demer JL. The Apt Lecture: Connective tissues reflect different
45. Chaudhuri Z, Demer JL. Medial rectus recession is as effective as mechanisms of strabismus over the life span. J AAPOS. 2014;
lateral rectus resection in divergence paralysis esotropia. Arch Oph- 18:309-315.
thalmol. 2012; 130:1280-1284.
53. Demer JL. Compartmentalization of extraocular muscle function.
46. Pineles SL, Laursen J, Goldberg RA, Demer JL, Velez FG. Function Eye (Lond.) 2014; 29:157-162.
of transected or avulsed rectus muscles following recovery using an
54. Shin A, Yoo LY, Demer JL. Independent active contraction of
anterior orbitotomy approach. J AAPOS. 2012; 16:336-341.
extraocular muscle compartments. Invest Ophthalmol Vis Sci.
47. Clark RA, Demer JL. Functional morphometry of horizontal rectus 2015; 56:199-206.
extraocular muscles during ocular duction. Invest Ophthalmol Vis
55. Demer JL, Clark RA. Magnetic resonance imaging demonstrates
Sci. 2012; 53:7375-7379.
compartmental muscle mechanisms of human vertical fusional ver-
48. Shin A, Yoo L, Chaudhuri Z, Demer JL. Independent passive gence. J Neurophysiol. 2015; 13:2150-2163.
mechanical behavior of bovine extraocular muscle compartments.
56. Peragallo JH, Pineles SL, Demer JL. Recent advances clarifying the
Invest Ophthalmol Vis Sci. 2012; 53:8414-8423.
etiologies of strabismus. J Neuroophthalmol. 2015; 35:185-193.
2015 Subspecialty Day  |  Neuro-Ophthalmology Section III: Double Vision and Nystagmus 21

“Words run together on the TV.” ated with spinocerebellar ataxia, progressive supranuclear palsy,
brainstem stroke, cerebellar and skull-based lesions, or head
Kimberly M Winges MD trauma. This phenomenon has also been reported in patients
with increased intracranial pressure, where the distinction
C ase between DI and bilateral CN VI palsies may be difficult.
On follow-up testing, this patient complained of difficulty
reading and running, with oscillopsia and frequent falls. She was
Clinical History and Exam found to have downbeat nystagmus and ataxic, wide-based gait.
A 68-year-old woman was referred by optometry for recurrent Her mother had developed similar symptoms without diagnosis
episodes of binocular horizontal diplopia that started 3 years years prior. Brain MRI showed cerebellar atrophy, and she was
ago and worsened over the last few months. She described words eventually diagnosed with spinocerebellar atrophy.
running together in the captions on the television screen, resolved Workup of DI should be based upon careful attention to any
by closing either eye. Diplopia was present only at distance, signs of cranial nerve palsy or historical/exam details suggesting
never at near, and it was not associated with fatigue or change in a neurologic cause (such as ataxia or presence of nystagmus, for
position. She denied new medications, lid drooping, trouble with example). When appropriate, neuroimaging can rule out brain-
speech or ambulation, dizziness, headache, jaw claudication, stem or other skull base lesions. Lab testing should be tailored
transient visual loss, or childhood strabismus. Her past medical to the history and exam findings that invoke suspicion of other
history was remarkable for pseudophakia O.U. and hypothyroid sources of diplopia, such as myasthenia gravis, thyroid disease,
disease. or temporal arteritis.
Eye exam revealed 20/20 BCVA O.U., normal near stereoacu- When no neurologic cause is suspected or found, DI is consid-
ity (8/9 circles by Titmus test), full confrontation visual fields, ered primary or idiopathic. In some cases of age-related distance
no relative afferent pupillary defect, and no proptosis or ptosis esotropia, mechanical changes in the orbit can be shown on high-
of either eye. Slitlamp biomicroscopy and dilated exams were resolution MRI that cause inferior displacement of the lateral
healthy, showing centered IOLs O.U. Extraocular motility test- rectus and breaking of the lateral rectus-superior rectus band.
ing revealed 5 PD of esotropia in primary gaze, which increased These involutional changes cause esotropia and hypotropia, or
to 8 PD in right and left gaze. Maddox rod testing did not elicit a the sagging eye syndrome, commonly associated with blepharop-
vertical deviation or ocular torsion. She was orthophoric at near. tosis and cyclovertical strabismus. This more recently recognized
Ductions were full, with normal saccades, slightly choppy pur- syndrome may be a source of DI in the elderly.
suit, and intact vestibulo-ocular reflex testing. Treatment of DI is similar to that of bilateral CN VI palsies,
including base-out prism correction and/or strabismus surgery. A
trial of 4 PD base-out Fresnel prism worked well for this patient
What would you do next? to alleviate her diplopia in distance spectacles.
1. Observe and place Fresnel prism on her glasses
2. Order ESR and CRP and start empiric prednisone References
­treatment
3. Order MRI brain w/wo contrast 1. Liu GT, Volpe NJ, Galetta SL. Eye movement disorders: third,
fourth, and sixth nerve palsies and other causes of diplopia and
4. Order TSH and noncontrast CT orbit
ocular misalignment. In: Neuro-ophthalmology: Diagnosis and
Management, 2nd ed. New York: Saunders Elsevier; 2010:491-550.
Clinical Course and Outcome 2. Kline LB, Foroozan R. Supranuclear and internuclear gaze path-
In summary, this is a case of adult-onset intermittent, binocular, ways. In: Neuro-Ophthalmology Review Manual, 7th ed. Thoro-
fare, NJ: SLACK Inc.; 2013:45-72.
horizontal diplopia, with exam revealing a relatively comitant
esotropia at distance, full ductions, and orthophoria at near. 3. Jacobson DJ. Divergence insufficiency revisited: natural history of
With an otherwise normal eye exam apart from pseudophakia, idiopathic cases and neurologic associations. Arch Ophthalmol.
the main differential diagnosis includes divergence insufficiency 2000; 118:1237-1241.
(DI) or subtle bilateral CN VI palsies. In this patient, the full 4. Chaudhuri Z, Demer JL. Sagging eye syndrome: connective tissue
ductions and normal saccade velocity made 6th nerve palsy less involution as a cause of horizontal and vertical strabismus in older
likely. Also, there were no other signs or symptoms of increased patients. JAMA Ophthalmol. 2013; 131(5):619-625.
intracranial pressure, which can cause bilateral CN VI palsy
5. Mittelman D. Age-related distance esotropia. J AAPOS. 2006;
due to downward displacement of the brain over the 6th nerves 10(3):212-213.
as they course against the skull base. Furthermore, onset was
insidious and not sudden, unlike the typical CN VI palsy. Other
considerations are broken down esophoria or thyroid eye dis-
ease, which is usually accompanied by other suggestive ocular
findings.
While nomenclature may vary, the term “divergence insuf-
ficiency” (DI) denotes a comitant esotropia that is worse at
distance than at near, with full ductions. Patients have binocular
horizontal diplopia at distance but not when viewing near tar-
gets. True neurologic divergence insufficiency or paralysis is a
supranuclear phenomenon, possibly due to disturbance of an
ill-defined divergence center in the brainstem. It can be associ-
22 Section III: Double Vision and Nystagmus 2015 Subspecialty Day  |  Neuro-Ophthalmology

“I see double when I get tired.” “I see double after my cataract

Marc J Dinkin MD surgery.”
Stacy L Pineles MD
C ase
C ase
History and Exam
A 45-year-old female photo editor with a medical history of History and Exam
hypertension and high cholesterol presented with double vision A 66-year-old man presents with decreasing vision in both eyes
when tired. Eleven months before presentation, her left eye began (left more than right) for about 3 years. He also notices glare at
deviating outward intermittently, especially when tired and at the night. His past ocular history is significant for a history of “lazy
end of a long work day. This was soon followed by intermittent eye” during childhood. He thinks he wore glasses and maybe
binocular vertical diplopia, worse in downgaze and worse when patched one eye during childhood to correct his lazy eye. He
tired and after a glass of wine. An MRI of brain and orbits was does not notice any diplopia at this time. The remainder of his
obtained by her primary medical doctor and was normal. past medical, surgical, social, and family history was noncon-
Patient was diagnosed by an ophthalmologist as experienc- tributory. On examination, his BCVA is 20/40 O.D. and 20/60
ing a breakdown of congenital strabismus and offered corrective O.S. His refraction is +2.50 O.U. He has a small esotropia. His
surgery. She opted instead to patch one eye and seek another slitlamp examination is normal except for 2+NS cataract O.D.
opinion and presented for neuro-ophthalmic consultation. and 2+NS/2+PSC O.S. His dilated fundus examination is normal.
She endorsed bouts of left upper eyelid ptosis, lasting a few He underwent uncomplicated cataract surgery in the left eye
weeks intermittently over the last year. and on postoperative Day 1, he began to notice binocular diplo-
Family history was significant for diabetes in both parents. pia. At that time, his BCVA was 20/40 O.D. and 20/25 O.S.
She was single and never smoked. She was on no medications
and had an allergy to penicillin.
On examination, visual acuity was 20/15 in right eye and What is the most likely etiology of his double vision?
20/20 in left eye. Pupils were equal in the dark, but in the light, 1. Extraocular muscle contracture after retrobulbar injection
the left pupil was 1 mm larger. Intraocular pressures, confronta- 2. Unmasked esotropia from thyroid eye disease
tional visual fields, and funduscopy were unremarkable. Extra- 3. Fixation switch diplopia
ocular movements appeared full, but cross-cover testing demon- 4. Monocular diplopia due to induced astigmatism
strated an incomitant exotropia worse in upgaze and left gaze.
Fusional amplitude in the vertical plane was 3 PD. Maddox rod
testing indicated a right hypertropia that was worse in upgaze Clinical Course and Outcome
and to the left, as well as in right head tilt. Saccades were slowed On further examination, the patient was found to have refractive
in the horizontal direction. errors of +2.50 O.D. and +0.50 O.S. His motility examination
There was left ptosis and Hertel exophthalmometry revealed demonstrated a comitant esotropia of 6 PD at distance and near.
measurements of 23 cm on the right and 21 cm on the left. His ocular rotations were normal. He was able to fuse with 6 PD
base out in front of his left eye. He was treated primarily with
Clinical Course prism glasses and then underwent cataract surgery in his right
eye. He continued to need the prism but could be weaned down
Cogan lid twitch sign was not detected, but there was signifi- from 6 PD to 2 PD to no prism over a period of a few months. As
cant fatigability with worsening of left ptosis after 1 minute of he began to fixate with his right eye, the diplopia resolved despite
upgaze. Enhanced ptosis (curtaining) was present bilaterally. The a residual esotropia of 4 PD.
remaining general neurological examination was normal, includ- The differential diagnosis for binocular diplopia after cataract
ing testing for fatigability of the deltoids and ability to count to surgery typically includes anesthetic myotoxicity from a retro-
30 in one breath. bulbar injection, pre-existing strabismus masked by the cataract
After 20 minutes of rest, the palpebral fissure and marginal (due to thyroid eye disease, myasthenia gravis, other forms of
reflex distance became equal at 10 and 5 mm, respectively, in strabismus), central disruption of fusion, optic aberrations, or
both eyes. disorders unique to a history of amblyopia such as elimination
Laboratory testing revealed elevated binding, blocking, and of suppression in the amblyopic eye due to a long-standing cata-
modulating acetylcholine receptor antibodies: 68.0 nmol/L (nor- ract, a change in the angle of strabismus leading to a drift outside
mal: 0.05 nmol/L), 45% and 83%, respectively. of the suppression scotoma, or fixation switch diplopia. This
MRI of the chest demonstrated a minimally enhancing soft patient was diagnosed with fixation switch diplopia because it
tissue mass of the thymus measuring 8.4x3.5 cm. Computed was clear that his diplopia began after his fixation was switched
tomography revealed calcification of the mass. A robotic thymec- from the right eye to the left eye. In this case, the patient’s domi-
tomy was performed, and the mediastinal mass contained both nant eye (O.D.) had poorer vision after the left eye underwent
thymic tissue and amyloid. cataract surgery and was corrected to 20/25. Once the right eye
The patient was treated with oral steroids for 3 months and was corrected to 20/20, the patient was able to regain fixation
experienced complete resolution of ptosis and diplopia. with the dominant eye and his diplopia resolved as his left eye
vision was moved back into his appropriate facultative suppres-
sion scotoma.
2015 Subspecialty Day  |  Neuro-Ophthalmology Section IV: Test Interpretation 23

Section IV: Test Interpretation Made

Ridiculously Simple

What Do I Do With This Visual Field? Should I Trust My Exam, or the OCT?
Gregory P Van Stavern MD M Tariq Bhatti MD

C ase C ase

History and Exam History and Exam

A 55-year-old woman presented to a general ophthalmologist A previously healthy 24-year-old woman experienced sudden
with a 1-year history of blurred vision in both eyes. She had a loss of vision of the left eye while jogging on a treadmill. Within
history of hypertension, which was well controlled, and was 45 minutes the vision improved but did not return to normal. She
otherwise healthy. Family history was notable for a sister with denied eye pain, headache, or any other systemic or neurologi-
glaucoma but was otherwise unremarkable. She did not smoke cal symptoms. The only medication she was taking was ethinyl
and only drank alcohol socially. She was using amlodipine for estradiol/norgestrel (oral contraceptive pills). She did not smoke
blood pressure control and zolpidem for sleep as needed. She had and had only an occasional alcoholic beverage. Family history
noticed more difficulty with reading and driving, particularly was unremarkable.
with left turns and left lane changes. The patient presented to a local emergency room and was
On initial examination, BCVA was 20/30 O.D., 20/25 O.S., evaluated by an ophthalmologist and admitted to the hospital for
attributed to mild cataracts. Pupils were normal, with no rela- management of the visual loss. Patient reports that she had blood
tive afferent pupillary defect noted. IOP was 19 O.D., 20 O.S. work, cranial MRI, and transesophageal echocardiogram that
Fundus examination showed flat optic discs, cup-to-disc 0.5 were all reported to be negative or normal. She was discharged
O.D., 0.45 O.S., with some thinning of the temporal rim. The from the hospital after 3 days and referred to a local retina spe-
remainder of the examination was unremarkable. Humphrey cialist. On her initial follow-up examination, visual acuity was
visual fields were performed. These were interpreted as showing noted to be 20/20 O.D. and hand motions O.S. An intravenous
an inferior altitudinal defect in the right eye and a superior arcu- fluorescein angiogram was interpreted as showing choroidal
ate defect in the left eye. The working diagnosis at that time was ischemia O.S. Approximately 3 months after the onset of visual
“normal-tension glaucoma vs. previous nonarteritic ischemic loss, vision was 5/200 O.S. with superior optic nerve pallor,
optic neuropathy (NAION).” The patient missed a follow-up resulting in a referral to the neuro-ophthalmology service.
appointment and returned nearly 9 months later. Visual acuity
was now 20/40 O.U. Her fundus examination showed possible
Clinical Course and Outcome
neuroretinal rim pallor O.U. Repeat Humphrey visual fields
showed worsened field loss. On the day of the neuro-ophthalmic visit, the patient stated that
the visual changes of the left eye were stable and the vision in the
right was normal. On examination, visual acuity was 20/20 O.D.
Clinical Course and Outcome
and 20/30 O.S. Color vision with the Ishihara pseudochromatic
The patient was referred to neuro-ophthalmology. The exami- plates was 10/10 O.D. and 7.5/10 O.S. There was a left rela-
nation was unchanged, but the field defect raised concern for a tive afferent pupillary defect. Orbital, ocular motility, IOP, and
chiasmal lesion. MRI of the brain and orbits with and without slitlamp biomicroscopy examinations were all normal. Fundu-
gadolinium was performed. This demonstrated a large, homo- scopic examination of the right eye was normal. In the left eye,
geneously enhancing mass compressing the optic chiasm and the the superior pole of the optic nerve was pale, with narrowing of
right intracranial optic nerve, most compatible with suprasellar the superotemporal arcade vessel. Automated perimetry demon-
meningioma. She underwent surgical resection of the tumor and strated a dense inferior altitudinal defect O.S. OCT retinal nerve
did well postoperatively, with partial recovery of field and visual fiber layer thickness was normal O.D. (96 µm) and thin supero-
acuity. temporally O.S. (57 µm). Macular OCT demonstrated thinning
of the inner retinal layers in the superior retina with parafoveal
disruption within the ellipsoid zone.
24 Section IV: Test Interpretation 2015 Subspecialty Day  |  Neuro-Ophthalmology

“I can’t get cocaine drops in my In any case of ptosis and/or anisocoria, further review of
systems and examination can help to refine the differential diag-
office!” nosis. Though not seen in our patient, ocular misalignment could
Heather E Moss MD PhD point toward third nerve palsy, myasthenia gravis, or cavernous
sinus syndrome. Accompanying numbness, weakness, or coordi-
C ase nation disturbance might suggest brainstem injury. Our patient
reported shoulder pain ipsilateral to his ophthalmic findings,
which was concerning for an associated process in the chest,
History and Exam cervical spine, or neck. His cocaine history, though remote, sug-
gested vascular etiologies.
A 67-year-old man in excellent health presented for evaluation of In this case the anisocoria worse in the dark and ptosis with
1 month of right eyelid drooping. He thought it got better in the normal levator function were sufficient to clinically diagnose
evening. He denied diplopia or change in vision. He had not had Horner syndrome, and workup was initiated to identify a causal
headaches, dyspnea, dysarthria, or dysphagia. etiology. If the exam is equivocal or if there are contraindications
On review of systems he noted right shoulder pain. He was to imaging, eye drop testing can be used to confirm a Horner
not taking any medications. He smoked 3 cigarettes each day. He syndrome diagnosis. Cocaine drops act presynaptically and cause
had a history of cocaine use, last 6 months prior to evaluation. less dilation of a pupil with sympathetic dysfunction than of a
On examination, visual acuity was 20/20 with each eye. Duc- pupil without sympathetic dysfunction. Apraclonidine, which
tions were full. The right pupil was 1 mm smaller than the left is more readily available than cocaine, acts postsynaptically to
pupil. There was no relative afferent pupillary defect. There was cause more dilation of a pupil with sympathetic dysfunction
2 mm of relative ptosis of the right eye. Anterior and posterior than of a pupil without sympathetic dysfunction. Literature sug-
ophthalmoscopic exams were unremarkable. gests that both tests have similar sensitivity and sensitivity for
Horner syndrome. Based on the mechanisms of action, cocaine is
What would you do next? theoretically more sensitive than apraclonidine in the hyperacute
setting, though reports suggest that this does not limit its use in
• MRI scan clinical practice. In our patient, apraclonidine testing had been
• Send to emergency department used by the referring provider, who reported that 30 minutes
• Refer to neuro-ophthalmology following instillation of 1 gtt. of 0.5% apraclonidine in each eye,
• Do further in office testing/examination the right pupil was 1 mm larger than the left. This confirmed a
diagnosis of right Horner syndrome.
Clinical Course and Outcome If there is a known causal explanation (eg, recent carotid
instrumentation, known recent lateral medullary stroke), then
Unilateral ptosis and miosis are concerning for a diagnosis of further evaluation may not be needed. However, this was not the
Horner syndrome. Other diagnostic considerations include con- case with our patient, so imaging was necessary to screen for eti-
current causes of isolated ptosis (eg, aponeurotic, myasthenia ologies requiring treatment. Complete evaluation of the sympa-
gravis, third nerve palsy) and anisocoria (eg, physiologic, tonic thetic chain includes brain imaging (MRI, not CT), neck imaging
pupil, third nerve palsy). Additional clinical examination can (MRI), carotid angiographic imaging (CTA or MRA, not carotid
quickly refine the diagnosis. ultrasound), and chest imaging (CT or MRI, not chest x-ray),
Further diagnostic information regarding anisocoria can be which can be refined or staged based on accompanying signs
easily obtained by comparing the relative anisocoria in light and and symptoms. Important etiologies requiring treatment include
dark environments. In this case, detailed pupil exam revealed brainstem stroke or tumor, Pancoast tumor in the lung apex,
that the right pupil was 1 mm smaller than the left pupil with the carotid pathology such as dissection, cavernous sinus pathology
room lights on and 1.5 mm smaller than the left pupil with the such as tumor, or orbital process. In our case, MRI of the brain
room lights off. This suggested that the right eye was not dilating and neck, MRA neck, and CT chest with contrast were obtained.
adequately due to sympathetic dysfunction. The chest CT showed a right lung apex mass. Biopsy was diag-
Further diagnostic information regarding ptosis can be nostic of small cell lung cancer.
obtained by measuring the position and function of the upper
eyelids. In this case, eyelid measurements included marginal
reflex distance 1 of 2 mm in the right eye and 4 mm in the left.
Levator function was normal and symmetric in both eyes with-
out curtain, twitch, or fatigue. This could be consistent with
aponeurotic ptosis or Müller muscle weakness due to sympa-
thetic dysfunction. Though not seen in this patient, another sign
sometimes seen in oculosympathetic injury is lower lid ptosis,
characterized by decreased marginal reflex distance 2.
2015 Subspecialty Day  |  Neuro-Ophthalmology Section IV: Test Interpretation 25

Mini-Talk: Bias in Testing—Do I Only Find What I

Thought Was There?
Harold E Shaw Jr MD

NOTES
26 Section IV: Test Interpretation 2015 Subspecialty Day  |  Neuro-Ophthalmology

“The MRI is abnormal; now what?” Everyone’s ESR Is High: Who Needs
Fiona E Costello MD a Biopsy?
Todd Alan Goodglick
C ase
C ase
History and Exam
History and Exam
History
A 30-year-old woman with recent headaches is admitted after Fifty-nine-year-old white woman referred for variable headache
2 generalized tonic-clonic seizures. Her comorbidities include on her left side for 3 months, without association to activity or
Crohn disease, for which she recently initiated treatment with position, pain around the ears and in throat. She specifically
infliximab. The patient stands 5 feet tall and weighs 260 lbs. denies jaw claudication. She also notes 2 episodes, 2 and 3 weeks
Over the past 4 weeks she has experienced a 30-lb. weight loss ago, of graying out of part of her peripheral vision in her left eye,
secondary to bloody diarrhea from active inflammatory bowel but it only lasted about a minute so she didn’t seek help. Her
disease. internist has previously obtained a noncontrast MRI of the head
She describes a week-long history of blurred vision in both and carotid Doppler study, which were normal.
eyes. She describes episodes of visual dimming in one or both Patient’s past medical history includes type 2 diabetes mel-
eyes that is often triggered by rapid position changes and hears a litus, hypertension, and generalized arthritis presently in a flare-
pulsing “heartbeat in her ears.” She denies diplopia. up, including the neck, which she attributes the headache to. She
was diagnosed with pneumonia 3 weeks ago, associated with
Examination fevers and mild congestive heart failure.
Visual acuity is 20/100 in the right eye and 20/80 in the left eye. Her visual acuities were 20/25 O.D., 20/30 O.S. The rest of
Pupils measure 4 mm in darkness and constrict to 3 mm in bright her examination was normal.
light with no relative afferent pupillary defect. The patient is
able to read 3/6 Hardy-Rand-Rittler pseudoisochromatic plates Clinical Course and Outcome
with each eye. Ocular motility and external ocular examination
are normal. The visual field testing and fundus examination are Below are possible laboratory results:
depicted in Figures 1 and 2.
The patient undergoes a cranial MRI scan with venography, 1 2 3 4
which demonstrates a partially empty sella, bilateral flattening of Sed rate 22 35 60 60
the globes, and tortuosity of the optic nerve sheaths. Initially, the C-reactive 0.5 5 0.5 5
MR venogram is reported as normal. protein

The four options are as follows: 1 = observe, 2 = grab for the bottle of prednisone
on the shelf, 3 = grab for the surgical scheduling sheet on the shelf, 4 = grab for the
glass of single malt scotch on the shelf.

The patient in question, on the young side for a reflexive

consideration of giant cell arteritis (GCA) (diagnostic criteria 50
years old or greater but peak incidence at 70-80), presents with
common symptoms that are neither textbook nor dismissible for
this disease (ie, vague but bothersome temporal headache, tran-
sient visual obscurations, generalized myalgias, and equivocal lab
results with other potential reasons that might explain them. As
is often the case the exam doesn’t demonstrate classic findings
(catastrophic vision loss, focal or diffuse signs of inflammation
along the superficial temporal arteries, pale optic nerve head
swelling).
Answer and Teaching Points
28 Section I: Vision Loss 2015 Subspecialty Day  |  Neuro-Ophthalmology

Section I: Vision Loss Made Ridiculously Simple

“I suddenly lost vision in one eye.” in all patients with optic neuritis to assess the risk for MS.
MS demyelinating plaques can be found throughout the brain
Marie D Acierno MD but have a predilection for the periventricular white matter
region in an ovoid configuration perpendicular to the periven-
Final Diagnosis tricular region and lateral borders of the corpus callosum. The
overall 15-year risk of developing MS after optic neuritis is
This young man has unilateral optic neuritis. 50% based on clinical criteria. However, the risk can be further
refined. In the absence of demyelinating lesions, the risk is low,
Teaching Points at 25%, while the risk is 72% when lesions are present.
If the clinical presentation has the typical features of an acute
Optic neuritis is an acute inflammatory disorder of the optic optic neuritis, spontaneous visual recovery usually begins in the
nerve commonly associated with multiple sclerosis. It is mani- first 4 to 6 weeks, with continued improvement and good visual
fest by acute, unilateral visual loss, eye pain, typically with eye prognosis by 6 to 12 months. Ninety-four percent recover to
movement, decreased color and/or decreased contrast, visual 20/40 or better, and 3% of patients remain with 20/200 or worse
field defect, and a relative afferent pupillary defect. Ninety-two visual outcome after 5 years, based on the Optic Neuritis Treat-
percent of patients have accompanying pain. Sixty-five percent of ment Trial (ONTT) results. However, those with visual recovery
patients have a normal appearing optic nerve, reflecting retrobul- still had residual deficits such as decreased contrast sensitivity.
bar disease, while 35% have optic disc edema. The clinical decision to manage and treat a patient with
Our patient presented with optic disc edema (rather diffuse / typical optic neuritis with steroids is often challenging. The
severe without hemorrhages), a less common presentation for ONTT was a multicentered, randomized, controlled clinical trial
acute, isolated optic neuritis. If a patient presents with optic disc designed to evaluate the efficacy and safety of oral prednisone
edema, it may be necessary to re-examine the patient in several (1 mg/kg daily for 2 weeks) vs. intravenous methylprednisolone
days to assess for development of macular exudates. This finding (250 mg 4 times daily for 3 days, followed by prednisone 1 mg/
establishes the diagnosis of neuroretinitis, which is not associ- kg daily for 11 days) compared with oral placebo for the treat-
ated with demyelinating disease and therefore does not warrant ment of acute optic neuritis. Primary outcome measures were
neuroimaging. Sarcoid can also present as a typical optic neuritis, contrast sensitivity and visual field, and secondary measures
usually with optic disc involvement. Visual recovery varies for were vision and color. In summary, the ONTT revealed the IV
sarcoid optic neuritis, but it often does not improve without steroid-treated patients recovered visual function faster within
steroid therapy. One should definitely consider Leber hereditary the first 4-6 weeks following onset of optic neuritis, but showed
optic neuropathy (LHON) in such a clinical presentation. LHON no statistical difference in final visual outcome from the IV ste-
may occur in both men and women, but it is more common in roid-treated patients and those receiving placebo. Oral steroids
young adult males. Patients with LHON may present with a are contraindicated for acute optic neuritis because of a higher
normal-appearing disc in the affected eye or with mild disc swell- rate of recurrence of optic neuritis.
ing with peripapillary telangiectasia. LHON is a painless visual Treatment varies among clinicians despite the ONTT. Some
loss resulting in a dense central scotoma in the affected eye. Only clinicians treat patients with 1 gm per day infused over 3 to 5
those LHON patients with specific mitochondrial mutations may days in an outpatient infusion center. Some use oral prednisone
experience partial or complete visual recovery after months or thereafter, while others have abandoned it. The potential side
years. Patients will usually acquire bilateral simultaneous visual effects and complications should be discussed with the patient
loss in weeks to months in the contralateral eye. prior to administration. Oral steroids alone are always contra-
The risk of developing MS following an acute optic neuritis is indicated for acute optic neuritis because of an increased rate
lower for those patients with severe optic disc swelling with hem- of recurrences of optic neuritis. But all patients with abnormal
orrhages or a macular star, absence of pain, vision reduced to no MRIs should be referred to the neurologist for further evalua-
light perception, and in males. tion and management for MS. Institution of disease-modifying
In a typical presentation of optic neuritis, blood laboratory therapy should be discussed.
testing and lumbar puncture are not indicated. If the clinical OCT of the nerve fiber layer is a useful supplementary test
course is unusual in any way, such as prolonged pain, lack of to measure optic nerve structure in patients with optic neuritis.
visual recovery within 4 to 6 weeks, recurrence within 2 months, OCT can quantify the initial swelling and subsequent atrophy of
or manifestation of other clinical findings, the presentation is the retinal nerve fiber layer as disc pallor develops at 6-8 weeks
considered atypical and a workup is pursued accordingly. following the onset of an acute, isolated optic neuritis. Often, the
Optic neuritis may be the first clinical sign of MS or it may optic atrophy can be subtle on funduscopic examination. The
occur in a patient with the established diagnosis of MS. Our OCT provides a quantitative measure of the retinal nerve fiber
patient’s MRI orbit imaging study demonstrates left optic nerve layer thickness that can document the degree of optic atrophy.
enhancement, which is helpful but not necessary for the diag-
nosis of optic neuritis. Contrast-enhanced imaging with fat sup-
pression technique allows optimal views of the optic nerves. MRI
brain/orbit imaging study with gadolinium should be considered
2015 Subspecialty Day  |  Neuro-Ophthalmology Section I: Vision Loss 29

Selected Readings C. Dry AMD

1. Basic and Clinical Science Course Section 5: Neuro-Ophthalmol- D. Macular edema
ogy, 2009-2010. San Francisco: AAO, 2009: 111-172.
1. Postoperative cystoid macular edema (CME)
2. Cleary PA, Beck RW, Anderson MM Jr, Kenny DJ, Backlund JY,
Gilbert PR. Design, methods, and conduct of the Optic Neuritis 2. Diabetic macular edema
Treatment Trial. Control Clin Trials. 1993; 14(2):123-142.
3. Uveitic CME
3. Comi G. Shifting the paradigm toward earlier treatment of multiple
sclerosis with interferon beta. Clin Ther. 2009; 31(6):1142-1157. 4. Systemic medications (thiazolidinediones, fingo-
limid, tamoxifen, taxanes, niacin, interferon)
4. Fisher JB, Jacobs FA, Markowitz CE, et al. Relation of visual func-
tion to retinal nerve fiber layer thickness in multiple sclerosis. Oph- 5. Ocular medications (prostaglandin analogs, epi-
thalmology 2006; 113:324-332. nephrine, timolol)
5. Gea Y. Multiple sclerosis: the role of MR imaging. AJNR Am J E. Infectious (toxoplasmosis, presumed ocular histo-
Neuroradiol. 2006; 27:1165-1176. plasmosis, diffuse unilateral subacute neuroretinitis)
6. Jirawuthiworavong GV, Miller AM, Fajardo D. Demyelinating F. Inflammatory (sarcoidosis, Vogt-Koyanagi-Harada
optic neuritis. 2015. EyeWiki website: eyewiki.org/demyelinat- syndrome, posterior scleritis, serpiginous chorioreti-
ing_optic_neuritis.
nopathy, autoimmune retinopathy)
7. Kappos L, Freedman MS, Polman CH, et al; BENEFIT Study
G. Retinitis pigmentosa and allied disorders
Group. Long-term effect of early treatment with interferon beta-1b
after a first clinical event suggestive of multiple sclerosis: 5-year H. Toxicity (hydroxychloroquine, chloroquine, thio-
active treatment extension of the Phase 3 BENEFIT trial. Lancet ridazine, chlorpromazine, quinine)
Neurol. 2009; 8(11):987-997.
I. Macular dystrophy (cone-rod dystrophy, Best dis-
8. McKinney AM, Lohman BD, SarikayaB, Benson M, Lee MS, Ben-
ease, Stargardt disease)
son MT. Accuracy of routine fat-suppressed FLAIR and diffusion-
weighted images in detecting clinically evident acute optic neuritis. J. Macular telangiectasia
Acta Radiol. 2013; 54:455-461.
K. White dot syndromes (AZOOR)
9. Optic Neuritis Study Group. The 5-year risk of MS after optic neu-
ritis: experience of the Optic Neuritis Treatment Trial. Neurology L. Nutritional vitamin A deficiency
1997; 49:1404-1413. 
M. Paraneoplastic syndromes
10. Optic Neuritis Study Group. High- and low-risk profiles for the
development of multiple sclerosis within 10 years after optic neuri- 1. Cancer-associated retinopathy (CAR)
tis. Arch Ophthalmol. 2003; 121:944-949.  2. Melanoma-associated retinopathy (MAR)
11. Optic Neuritis Study Group. Multiple sclerosis risk after optic neu- N. Tumor-ocular melanoma
ritis: final Optic Neuritis Treatment Trial follow-up. Arch Neurol.
2008; 65(6):727-732. O. Radiation-induced retinopathy
II. Optic Nerve
A. Glaucoma

“I am slowly losing vision in one of B. Compressive lesions affecting the optic nerve ante-
rior to the chiasm (cerebral meningioma, aneurysm)
my eyes.”
C. Optic nerve meningioma / optic nerve glioma
Guy V Jirawuthiworavong MD
D. Toxic optic neuropathy (ethambutol, linezolid)
Final Diagnosis E. Nutritional optic neuropathy (post-gastric bypass-
B12, folate, thiamine)
Acute zonal occult outer retinopathy (AZOOR)
F. Hereditary optic neuropathy-dominant optic atro-
phy (Kjer’s)
Teaching Points
The fundus findings of retinal pigmented epithelial atrophy
In summary, this patient presents with unilateral visual loss with
narrows the differential diagnosis to retinal causes. OCT of the
a relative afferent pupillary defect, pericentral scotoma, and sec-
macula shows thinning of the outer retina, but there is no vit-
toral retinal pigmented epithelial atrophy corresponding to visual
reomacular traction, intraretinal fluid, or subretinal fluid. The
field, OCT, and fluorescein angiography findings, consistent
patient’s history of photopsias, nyctalopia, scotoma, and gradual
with the diagnosis of AZOOR.
progression is consistent with conditions such as retinitis pigmen-
Broad differential diagnosis of gradual, unilateral visual loss:
tosa, cone-rod dystrophy, white dot syndrome, autoimmune reti-
I. Retina nopathy, or a paraneoplastic syndrome. Blind spot enlargement
can be the first visual field defect seen in retinitis pigmentosa.
A. Vitreoretinal interface disorders (epiretinal mem-
However, asymmetry of fundus findings and a relative afferent
brane, vitreomacular traction, macular hole)
pupillary defect (RAPD) are exceptions to the rule in patients
B. Central serous chorioretinopathy with retinitis pigmentosa, as well as in cone-rod dystrophy and
30 Section I: Vision Loss 2015 Subspecialty Day  |  Neuro-Ophthalmology

autoimmune retinopathy (AIR). Color vision is not spared in “My doctor says I might have
cone-rod dystrophy. CAR, MAR, and AIR patients have attenu-
ated vasculature but otherwise have no other typical retinal find- glaucoma.”
ings. MAR patients usually present with a preceding diagnosis Jacinthe Rouleau MD
of melanoma. Underlying cancer screening and the presence of
antiretinal antibodies against retinal proteins and retinal tissue
can help differentiate CAR, MAR, and AIR. This patient’s left Final Diagnosis
eye shows peripapillary changes seen on fluorescein angiography. Prior nonarteritic anterior ischemic optic neuropathy
As a side note, Stargardt disease tends to spare the peripapillary
retina and the fovea, and the light-colored yellow flecks found in
Stargardt disease rarely become hyperpigmented. Teaching Points
AZOOR is an idiopathic inflammatory syndrome that affects 1. Be aware that various optic neuropathies can mimic glau-
young women more than men. AZOOR patients may complain comatous visual fields or cupping.
of gradual loss of vision over time with constant photopsias. 2. Clues that raise the suspicion of nonglaucomatous cupping
They often present with an enlarged blind spot that later pro- are pallor of the rim, reduced central acuity or color vision
gresses into a temporal / zonal visual field defect. This condition loss out of proportion to disc cupping, atypical visual field
can affect one or both eyes and tends to be asymmetric in presen- defects, discordance between visual fields and cupping,
tation. Central vision can be spared, and there is minimal RAPD marked relative afferent pupillary defect, and patient age
at onset. Patients present acutely without any retinal changes on less than 50 years old.
exam, and as a result, the diagnosis is often made many years 3. When optic atrophy is suspected to be from an old nonar-
later as the RPE changes are noted in follow-up. Patient’s family teritic anterior ischemic optic neuropathy (NAION) but
members can have an underlying autoimmune condition. prior optic nerve edema cannot be documented, appropri-
AZOOR is diagnosed by history and retinal exam and can ate imaging of the orbits is recommended to eliminate a
be confirmed by visual field testing, fluorescein angiogram, and compressive or infiltrative lesion.
OCT. The retinal findings on OCT and fluorescein angiogram
correspond topographically to the locations of the visual field
defect. These field defects tend to be peripapillary or contiguous Selected Readings
with the optic nerve. The newest imaging modality of fundus 1. Greenfield DS, Siatkowski RM, Glaser JS, Schatz NJ, Parrish RK
autofluorescence can show characteristic zones of hyperfluores- 2nd. The cupped disc: who needs neuroimaging? Ophthalmology
cence at the leading edge of the AZOOR. It is postulated that 1998; 105:1866-1874.
AZOOR is either an autoimmune dysregulatory condition or 2. Fraser CL, White AJ, Plant GT, Martin KR. Optic nerve cupping
a viral infectious disease entering the optic disc, but its etiology and the neuro-ophthalmologist. J Neuroophthalmol. 2013; 33:377-
remains to be determined. 389.
Unlike AZOOR, retinitis pigmentosa (RP) can present at any
3. Golnik K. Nonglaucomatous optic atrophy. Neurol Clin. 2010;
age and tends to follow the rules of mendelian genetics, except 28:631-640.
in simplex RP. The common visual field defect is a ring scotoma
but, as mentioned earlier, can uncommonly present with an 4. Atkins EJ, Bruce BB, Newman NJ, Biousse V. Treatment of nonar-
enlarged blind spot on visual field testing. Fundus findings of teritic anterior ischemic optic neuropathy. Surv Ophthalmol. 2010;
55:47-63.
bone spicules are sine qua non for RP, whereas AZOOR may or
may not have any hyperpigmented spots. 5. Lee AG, Chau FY, Golnik KC, Kardon RH, Wall M. The diagnos-
tic yield of the evaluation for isolated unexplained optic atrophy.
Ophthalmology 2005; 112:757-759.
Selected Readings
1. Ryan SJ. Retina, vols. 1 and 2. 5th ed. London: Saunders-Elsevier;
2013.
2. Yanuzzi LA. The Retina Atlas. London: Saunders-Elsevier; 2010.
3. Nussenblatt RB, Whitcup SM. Uveitis: Fundamentals and Clinical
Practice. 4th ed. London: Mosby-Elsevier; 2010.
4. Makri OE, Georgalas I, Georgakopoulos CD. Drug-induced macu-
lar edema. Drugs 2013; 73(8):789-802.
5. Mrejen S, Khan S, Gallego-Pinazo R, et al. Acute zonal occult outer
retinopathy: a classification based on multimodal imaging. JAMA
Ophthalmol. 2014; 132(9):1089-1098.
2015 Subspecialty Day  |  Neuro-Ophthalmology Section I: Vision Loss 31

“I lose my vision and then it comes “I’m losing vision in both eyes.”
back.” John J Chen MD
Jeffrey Bennett MD PhD
Final Diagnosis
Final Diagnosis This patient had both normal-tension glaucoma and compressive
Vasospastic amaurosis fugax causing transient monocular vision optic neuropathy, with the former leading to a delay in the diag-
loss nosis of the compressive element.

Teaching Points Teaching Points

Retinal vasospasm is a rare cause of amaurosis fugax. During an 1. Compressive optic neuropathy causes a painless, progres-
episode, funduscopic findings include arterial and venous nar- sive decline in vision, often affecting central vision first.
rowing due to reduced arterial blood flow, “box-carring” of the With compressive optic neuropathy, the optic nerves
blood column, and collapse of the retinal veins. Between events, initially appear normal without edema unless the lesion
the fundus exam is normal. Rarely, events may result in vascular is anterior or causes obstructive hydrocephalus. Gradual
retinopathy or optic neuropathy. pallor of the optic nerve with thinning of the retinal nerve
As vasospastic amaurosis is rare, the diagnosis should be fiber layer and ganglion cell layer is expected if not treated.
made only after excluding visual and life-threatening vascular Because compressive optic neuropathy is generally revers-
conditions in susceptible individuals. Critical conditions that are ible if found early, progressive painless vision loss is a sign
important to consider in the patient with transient monocular of retrobulbar compression until proven otherwise.
vision loss include carotid stenosis, cardiac emboli (valvular dis- 2. Patients can have two pathologies. This patient had
ease and paradoxical emboli), hypercoagulable states (antiphos- normal-tension glaucoma with advanced cupping, which
pholipid antibody syndrome), and vasculitis. In many, but not delayed the diagnosis of compressive optic neuropathy.
all instances, fundus findings may provide important clues such While Occam’s razor of diagnostic parsimony typically
as cholesterol, calcific, or platelet-fibrin emboli, or choroidal holds true in medicine, we have to keep in mind Hickam’s
changes (Elschnig spots). Carotid Doppler ultrasound, erythro- dictum: “Patients can have as many diseases as they damn
cyte sedimentation rate, C-reactive protein, and echocardiogra- well please.”1
phy should be performed in all patients with vascular risk factors 3. Compressive lesions can cause cupping of the nerve in
who have transient monocular vision loss. MR angiography some instances.2,3 Therefore, neuroimaging is required to
should be added if there is any concern for carotid dissection. evaluate for nonglaucomatous optic atrophy in patients
Since vasospastic amaurosis has been associated with polyarteri- with cupping from presumed normal-tension glaucoma
tis nodosa and eosinophilic vasculitis, additional autoimmune who have atypical features, such as an age younger than
serologies (ANA and ANCA) should be considered in suspicious 50 years old, decreased central visual acuity, pallor of the
cases. Also, given the reported association between vasospastic residual neuroretinal rim, visual field defects respecting
amaurosis and cluster / migraine headaches, a careful headache the vertical midline, color vision deficits, or symptoms of
history may be helpful in making a diagnosis when other causes hypothalamic-pituitary dysfunction.4
have been excluded. 4. A central or cecocentral scotoma on visual field testing is
Vasospastic amaurosis is exquisitely responsive to calcium almost always pathologic. Thompson and colleagues stud-
channel blockade. Verapamil 240-360 mg daily is often sufficient ied the ability to volitionally create functional visual fields
to resolve the recurrent events. and a cecocentral scotoma was the hardest to create.5

Selected Readings References

1. Hilliard AA, Weinberger SE, Tierney LM Jr., Midthun DE, Saint
1. Bernard GA, Bennett JL. Vasospastic amaurosis fugax. Arch Oph-
S. Clinical problem-solving: Occam’s razor versus Saint’s Triad. N
thalmol. 1999; 117(11):1568-1569.
Engl J Med. 2004; 350(6):599-603.
2. Petzold A, Islam N, Plant GT. Video reconstruction of vasospastic
2. Bianchi-Marzoli S, Rizzo JF 3rd, Brancato R, Lessell S. Quantita-
transient monocular blindness. N Engl J Med. 2003; 348(16):1609-
tive analysis of optic disc cupping in compressive optic neuropathy.
1610.
Ophthalmology 1995; 102(3):436-440.
3. Hill DL, Daroff RB, Ducros A, Newman NJ, Biousse V. Most cases
3. Kupersmith MJ, Krohn D. Cupping of the optic disc with com-
labeled as “retinal migraine” are not migraine [review]. J Neur-
pressive lesions of the anterior visual pathway. Ann Ophthalmol
oophthalmol. 2007; 27(1):3-8.
(Skokie). 1984; 16(10):948-953.
4. Piette SD, Sergott RC. Pathological optic-disc cupping. Curr Opin
Ophthalmol. 2006; 17(1):1-6.
5. Thompson JC, Kosmorsky GS, Ellis BD. Field of dreamers and
dreamed-up fields: functional and fake perimetry. Ophthalmology
1996; 103(1):117-125.
32 Section I: Vision Loss 2015 Subspecialty Day  |  Neuro-Ophthalmology

“Can my child see?” Teaching Point 2

Once the diagnosis of optic nerve hypoplasia is made, whether
Gena Heidary MD PhD bilateral or unilateral, further testing including neuroimaging
and an endocrinologic evaluation should be performed to assess
The presentation will include fundus photos, MRI findings sug-
for features that would support the diagnosis of septo-optic
gestive of septo-optic dysplasia, and endocrine workup. In addi-
dysplasia. These include absent septum pellucidum, dysgenesis /
tion, I will provide recent follow-up details including VA and
agenesis of the corpus callosum, and pituitary abnormalities. In
treatment of strabismus to document the natural history of optic
the setting of septo-optic dysplasia, endocrine dysfunction may
nerve hypoplasia.
occur in spite of a normal radiographic appearance of the pitu-
itary. Most commonly, defects in growth hormone are identified;
Final Diagnosis however, panhypopituitarism may occur.
Visual impairment secondary to bilateral optic nerve hypoplasia
in the setting of septo-optic dysplasia Selected Readings
1. Borchert M. Reappraisal of the optic nerve hypoplasia syndrome. J
Teaching Points Neuroophthalmol. 2012; 32:58-67.
2. Mohney BG, Young RC, Diehl N. Incidence and associated endo-
Teaching Point 1 crine and neurologic abnormalities of optic nerve hypoplasia.
In an infant with subnormal vision for age, a framework for JAMA Ophthalmol. 2013; 131:898-902.
approaching the exam is to consider several general categories: a 3. Ahmad T, Borchert M, Geffner M. Optic nerve hypoplasia and
structural basis for visual impairment (eg, optic nerve hypopla- hypopituitarism. Pediatr Endocrinol Rev. 2008; 5:772-777.
sia, congenital cataracts), an inherited retinal dystrophy / degen-
erative process, cortical visual impairment, or delayed visual 4. Ahmad T, Garcia-Filion P, Borchert M, Kaufman F, Burkett L, Gef-
fner M. Endocrinological and auxological abnormalities in young
maturation. In this case, the clinical findings on the examination
children with optic nerve hypoplasia: a prospective study. J Pediatr.
revealed abnormalities of the optic nerves, providing the etiology
2006; 148:78-84.
for the poor visual behavior. Because of the bilateral involve-
ment, the baby presented with nystagmus; in contrast, children 5. Garcia-Filion P, Fink C, Geffner ME, Borchert M. Optic nerve
who harbor unilateral optic nerve hypoplasia will commonly hypoplasia in North America: a re-appraisal of perinatal risk fac-
present with a sensory strabismus. tors. Acta Ophthalmol. 2010; 88:527-534.
2015 Subspecialty Day  |  Neuro-Ophthalmology Section II: Eye Pain and Headache 33

Section II: Your “What” Hurts? Eye Pain and

Headache Made Ridiculously Simple

“Worst headache of my life!” “My head hurts for days on end.”

S Tonya Stefko MD John H Pula MD

Final Diagnosis Final Diagnosis

Pituitary apoplexy Horner syndrome in a patient with cluster headaches

Teaching Points Teaching Points

Because the pituitary gland sits directly inferior to the optic There are several different causes of painful Horner syndrome.
chiasm, any enlargement of the gland can lead to a chiasmal syn-
Our patient’s most pertinent finding was a Horner syndrome.
drome. As in any situation, a slowly growing mass will produce
When working up Horner syndrome, particularly when pain-
fewer symptoms than a rapidly expanding one. Depending on
ful, we recall that the sympathetic pathway to the eye consists
the patient’s specific anatomy and the anatomy of the tumor,
of three “orders.” Wallenberg syndrome (lateral medullary syn-
however, patients may have a myriad of other effects involv-
drome) due to vertebral dissection can cause a painful first-order
ing the optic nerves, upper cranial nerves, and optic tracts. In
Horner syndrome but would be expected to have other features
pituitary apoplexy, the cells of the tumor infarct and/or bleed
(eg, acute vestibular syndrome or crossed sensory loss). A painful
and very quickly put pressure upward on the diaphragma and
Horner syndrome will usually be postganglionic (third order).
laterally toward the cavernous sinuses. This is thought to be due
The postganglionic sympathetic pathway traverses the carotid
to intrinsic marginal perfusion combined with high metabolic
artery, skull base, cavernous sinus, and orbital apex. Painful
demands. It can cause the classic “thunderclap” headache or a
postganglionic, nonisolated Horner syndrome etiologies include
more insidious onset of diplopia, ptosis, decreased vision, and
Tolosa-Hunt syndrome (orbital pseudotumor), skull-based
light sensitivity evolving over hours to days. Headache is present
nasopharyngeal carcinoma or inflammatory lesions, or orbital
> 95% of the time, and aberration of extraocular movements
apex syndrome. These syndromes’ other clinical features will be
occurs in up to 75% of patients. Decrease in visual fields and,
specific to their location. An isolated, painful Horner syndrome
slightly less commonly, visual acuities are found in roughly half
mainly either involves the region of the superior cervical ganglion
of patients.
and internal carotid artery or presents without imaging abnor-
The incidence of apoplexy in pituitary tumors is 2%-12%
malities (as in the primary headache disorders).
(most commonly in nonfunctioning adenomas). It is the initial
Considering this, the differential diagnosis for isolated painful
presentation of the tumor in about 80% of patients. There are
Horner syndrome includes:
several known associations with apoplexy, including cardiac sur-
gery, insulin infusion, transient increased intracranial pressure, • The trigeminal autonomic cephalgias (TACs)
initiation of anticoagulation, and hypo- or hyperperfusion states. – Hemicrania continua
Surgical decompression of the optic apparatus, preferably – Paroxysma hemicrania
from a ventral approach (trans-sphenoidal or expanded endona- – SUNA/SUNCT (short-lasting unilateral neuralgiform
sal), results in improvement of visual deficits in more than 75% headaches with autonomic symptoms / short-lasting
of patients whose symptoms have been present for less than a unilateral neuralgiform headaches with conjunctival
week. If the main ophthalmic sequela is ophthalmoplegia, most injection and tearing)
patients improve even with nonsurgical management. Surgical – Cluster headache
treatment of strabismus should be delayed by 6-12 months to • Internal carotid artery dissection
ensure that natural recovery is complete. • Raeder syndrome
The trigeminal autonomic cephalgias are primary headache
Selected Readings disorders. Raeder syndrome is also called oculopupillary sym-
pathetic paralysis and is caused by lesion in the middle cranial
1. Oldfield EH, Merrill MJ. Apoplexy of pituitary adenomas: the
perfect storm. J Neurosurg. 2015; 122(6):1444-1449. fossa. A carotid dissection may be otherwise nonfocal. Distin-
guishing between these causes of an isolated painful Horner
2. Fraser CL, Biousse V, Newman NJ. Visual outcomes after treatment syndrome relies on both clinical and paraclinical investigation,
of pituitary adenomas. Neurosurg Clin N Am. 2012; 23(4):607- which are described next.
619.
3. Briet C, Salenave S, Chanson P. Pituitary apoplexy. Endocrinol Cluster headache has certain features, which distinguish it from
Metab Clin North Am. 2015; 44(1):199-209.
other similar syndromes.
Perhaps the first description of cluster headache was by the Brit-
ish neurologist Dr. Wilfred Harris. The seminal case described
by Harris highlighted “a man, age 47... pain struck him suddenly
34 Section II: Eye Pain and Headache 2015 Subspecialty Day  |  Neuro-Ophthalmology

across the left temple and forehead, and lasted for three-quarters “My eye just aches all the time.”
of an hour, like an ‘electric battery,’ while his face became
flushed and he felt faint. The neuralgia recurred thrice daily, at Rod Foroozan MD
about eight-hour intervals, for six weeks, and then disappeared
entirely for two years. Ever since his first attack he had left cervi- Final Diagnosis
cal sympathetic paralysis, there being slight ptosis, with a small
pupil.”1 Greater occipital neuralgia
The International Classification of Headache Disorders2
defines cluster headaches as having “a sense of restlessness or Teaching Points
agitation,” as well as conjunctival injection / lacrimation, nasal
congestion / rhinorrhea, eyelid edema, forehead and facial flush- 1.  Highlights of the International Headache Society diagnostic
ing and sweating, ear fullness, or Horner syndrome. Headaches criteria for greater occipital neuralgia include pain that is
are severe, unilateral, orbital or supraorbital / temporal, and recurrent, severe, and shooting or stabbing in quality. Other
occur between 8/day to every other day and last 15-180 minutes criteria include dysesthesia or tenderness of the scalp.1
each. The timing of the pain distinguishes it from the other tri- Symptoms from greater occipital neuralgia overlap other head-
geminal autonomic cephalgias. SUNCT/SUNA neuralgia lasts ache syndromes. The pain is thought to be caused by irritation
only seconds. Paroxysma hemicrania usually lasts 10-20 minutes, of the greater occipital nerve with multiple potential sites from
and hemicrania continua may last for days or more.3 surrounding tissue.2,3 The distinction from other headache syn-
During the typical 6-12 week cluster period, the headaches dromes can be difficult but is aided by criteria outlined by the
occur with clockwork regularity. Once a cluster period has com- International Headache Society, 3rd edition.
pleted, it may recur over a variable amount of time. On the other The anatomy of the greater occipital nerve and its relation-
hand, the Horner syndrome may not resolve after the cluster, ship to the surrounding soft tissue is variable, but the nerve com-
and in fact may never resolve in some cases. Response to treat- monly originates from the medial branch of the dorsal ramus of
ments also somewhat distinguishes cluster headache from other C2. The greater occipital nerve then ascends between the inferior
headache syndromes. Both alcohol and smoking can be headache oblique capitis muscle and semispinalis capitis and pierces the
triggers. Abortive treatments include inhaled high-flow oxygen semispinalis muscle. It then runs rostrolaterally and deep to the
for 10-15 minutes, which can completely relieve pain. Triptans trapezius muscle and pierces the aponeurosis of the trapezius
(eg, sumatriptan, zolmitriptan) provide acute pain relief during slightly inferior to the superior nuchal ridge, where it becomes
a cluster attack. Steroids (oral prednisone for 10-12 days) pro- subcutaneous and lies medial to the occipital artery. Branches
vide a bridge to prophylaxis, which often consists of verapamil, then supply cutaneous sensation to the posterior scalp from the
~240 mg daily in divided doses. external occipital protuberance to the vertex. Please see Figures
1 and 2 from reference #3 listed below for the pertinent anatomy
A painful Horner syndrome is a carotid dissection until proven
and potential sites of compression of the greater occipital nerve.3
otherwise.
Although this patient ended up having cluster headaches, one 2.  The eye examination should not reveal other causes for pain,
clinical pearl to remember is that in the correct clinical context, a and other primary (such as migraine) and secondary (giant cell
painful Horner syndrome should be considered a carotid dissec- arteritis, cervical spine disease) headache syndromes should be
tion until proven otherwise. There may be no other neurologic excluded by history, physical examination, and ancillary testing.
signs, and in these cases the isolated presentation especially Irritation of the greater, lesser, and third occipital nerves can all
mimics a cluster headache. Up to 20% of spontaneous carotid lead to symptoms categorized as occipital neuralgia. Pain may
dissections have a Horner syndrome,4 and 91% of carotid artery occur in the frontal area or the orbit through trigeminocervical
dissections that have a Horner syndrome are painful. Diagnosis interneuronal connections in the trigeminal spinal nuclei. When
is especially important because without treatment to prevent greater occipital neuralgia involves the orbit, the eye may be the
thromboembolism, the risk of stroke nears 20%.5 presumed site of pathology; however, the eye examination does
not reveal any abnormalities that would cause pain.4 Degenera-
References tive conditions involving the cervical spine can cause pain in a
similar pattern to occipital neuralgia, and in these patients, imag-
1. Harris W. Neuritis and Neuralgia. London: Humphrey Milford, ing of the skull base and cervical spine should reveal an abnor-
Oxford University Press; 1926.
mality.
2. Headache Classification Committee of the International Headache
Society. The International Classification of Headache Disorders, 3.  Relief of pain along the course of the greater occipital nerve
2nd ed. Cephalalgia 2004; 24:1-160. with an injection of local anesthetic helps suggest the diagnosis
3. May A. Diagnosis and clinical features of trigemino-autonomic
but is not pathognomonic, as other headache syndromes such
headaches. Headache 2013; 53:1470-1478. as migraine may be relieved by these injections.
The pain from occipital neuralgia may respond to oral agents
4. Glaser JS. Neuro-ophthalmology. Philadelphia: Lippincott Williams
such as gabapentin, carbamazepine, and tricyclic antidepres-
& Wilkins, 1999.
sants. However, injection of local anesthetic (typically lidocaine
5. Nautiyal A, Singh S, DiSalle M, O’Sullivan J. Painful Horner syn- or bupivacaine) has been thought to be more likely to relieve the
drome as a harbinger of silent carotid dissection. PLoS Med. 2005; pain from occipital neuralgia, but may also relieve pain from
2(1):e19. migraine and other headache syndromes. The course of the
greater occipital nerve can be estimated by finding the external
occipital protuberance and moving about 2 cm laterally and
2015 Subspecialty Day  |  Neuro-Ophthalmology Section II: Eye Pain and Headache 35

2 cm inferiorly. Palpation for pulsation and aspiration prior to “The light!! It hurts my eyes!!”
injection helps avoid involvement of the occipital artery. Some
authors have suggested mixing corticosteroids with local anes- Bradley J Katz MD
thetic, although there is no proof that this adds additional ben-
efit. Injection of botulinum toxin in the same anatomic area has Discussion
also been reported to limit the pain from greater occipital neural-
gia in a small group of patients. Photophobia, an abnormal intolerance to light, is associated with
Some patients may not respond to oral agents or local anes- a number of ophthalmic and neurologic conditions. However,
thetic injections. Neuromodulation using high-voltage radio in the presence of a normal neuro-ophthalmic examination,
frequency has been reported to improve pain, and occipital nerve the most common conditions associated with photophobia are
stimulation using an implanted stimulator has also been noted to migraine, blepharospasm, and traumatic brain injury. Recent
be effective for some refractory patients. Surgical decompression evidence indicates that the intrinsically photosensitive retinal
has been noted to be curative in some patients. ganglion cells play a key role in the pathophysiology of photo-
phobia. Although pharmacologic manipulation of intrinsically
The International Headache Society diagnostic criteria for photosensitive retinal ganglion cells may be possible in the
occipital neuralgia1 future, current therapies are directed at optical modulation of
these cells.
A. Unilateral or bilateral pain fulfilling criteria B-E
B. Pain is located in the distribution of the greater, Teaching Points
lesser and/or third occipital nerves.
1. Most patients with light sensitivity do not have an ocular
C. Pain has two of the following three characteristics: problem (eg, iritis).
1. Recurring in paroxysmal attacks lasting from a 2. Most patients with light sensitivity have migraine,
few seconds to minutes although it may be undiagnosed or misdiagnosed.
3. The purpose of the ophthalmic exam is to rule out other
2. Severe intensity light sensitive conditions, such as dry eye and blepharo-
3. Shooting, stabbing, or sharp in quality spasm.
4. Management includes optical treatments for indoor and
D. Pain is associated with both of the following: outdoor light sensitivity and referral to a headache special-
1. Dysesthesia and/or allodynia apparent during ist or neurologist.
innocuous stimulation of the scalp and/or hair
2. Either or both of the following: Selected Readings
a. Tenderness over the affected nerve branches 1. Blackburn MA, Lamb R, Digre KB, et al. FL-41 tint improves blink
frequency, light sensitivity, and functional limitations in patients
b. Trigger points at the emergence of the greater with benign essential blepharospasm. Ophthalmology 2009;
occipital nerve or in the area of distribution of 116:997-1001.
C2 2. Digre KB, Brennan KC. Shedding light on photophobia. J Neur-
E. Pain is eased temporarily by local anesthetic block oophthalmol. 2012; 32:68-81.
of the affected nerve. 3. Güler AD, Ecker JL, Lall GS, et al. Melanopsin cells are the prin-
cipal conduits for rod-cone input to non-image-forming vision.
F. Not better accounted for by another ICHD-3 diag-
Nature 2008; 453:102-105.
nosis
4. Hattar S, Liao HW, Takao M, Berson DM, Yau KW. Melanopsin-
containing retinal ganglion cells: architecture, projections, and
References intrinsic photosensitivity. Science 2002; 295:1065-1070.
1. The International Classification of Headache Disorders, 3rd ed. 5. Kawasaki A, Kardon RH. Intrinsically photosensitive retinal gan-
(beta version). Cephalalgia 2013; 33:629-808. glion cells. J Neuroophthalmol. 2007; 27:195-204.
2. Dougherty C. Occipital neuralgia. Curr Pain Headache Rep. 2014; 6. Noseda R, Kainz V, Jakubowski M, et al. A neural mechanism for
18:411. exacerbation of headache by light. Nat Neurosci. 2010; 13:239-
3. Cesmebasi A, Muhleman MA, Hulsberg P, et al. Occipital neural- 245.
gia: anatomic considerations. Clin Anat. 2015; 28:101-108. 7. Noseda R, Burstein R. Advances in understanding the mechanisms
4. Lee AG, Brazis PW. The evaluation of eye pain with a normal ocu- of migraine-type photophobia. Curr Opin Neurol. 2011; 24:197-
lar exam. Semin Ophthalmol. 2003; 18:190-199. 202.
36 Section II: Eye Pain and Headache 2015 Subspecialty Day  |  Neuro-Ophthalmology

“It hurts when I talk, and this cough of patients with biopsy-proven GCA, often in association with
other systemic symptoms or elevated CRP, as seen in our patient.
won’t go away.” Early recognition of dry cough in an elderly patient as a potential
Gabrielle R. Bonhomme MD symptom of GCA, particularly when in association with elevated
inflammatory markers or ocular findings such as AION, and
prompt temporal artery biopsy, may prevent delay of diagnosis
Final Diagnosis of GCA, and resultant vision loss.7
Temporal arteritis presenting with persistent cough, trismus, and
transient diplopia. Teaching Points
1. Temporal arteritis (GCA) should be considered in the dif-
Discussion ferential diagnosis when an elderly patient presents with
Temporal arteritis (GCA) is a medium to large vessel vasculitis new-onset headache.
that commonly presents with visual symptoms due to anterior 2. Recognition of less common, non-ocular signs of ischemia,
ischemic optic neuropathy (AION) (94%) and classic constitu- such as cough, trismus, and jaw claudication, is crucial to
tional symptoms of new-onset headache, jaw claudication, scalp the early diagnosis and therefore timely treatment of GCA.
tenderness, and polymyalgia rheumatica (PMR). The incidence 3. Occult GCA should be suspected in patients over the age
of GCA increases in patients older than 50 years of age, ranging of 50 years with AION and the above symptoms, even in
from 18 to 27 cases per 100,000 in people over 50 years of age. the absence of abnormal inflammatory markers such as
Genetic associations with HLA-DR4 and HLA-DRB1 exist.1 ESR and CRP.
The American College of Rheumatology (ACR) requires 3 of
the following 5 criteria for diagnosis: References
1. Age of 50 year or older 1. Hunder GG, Bloch DA, Michel BA, et al. The American College of
2. New headache Rheumatology 1990 criteria for the classification of giant cell arteri-
3. Temporal artery abnormality (tenderness to palpation or tis. Arthritis Rheum. 1990; 33(8):1122-1128.
decreased pulsation)
2. Hayreh SS, Podhajsky PA, Zimmerman B. Occult giant cell arteritis:
4. ESR > 50 mm/h
ocular manifestations. Am J Ophthalmol. 1998; 125(6):893.
5. Abnormal findings on temporal artery biopsy (evidence of
vasculitis)1 3. Murchison AP, Gilbert ME, Bikyk JR, et al. Validity of the Ameri-
can College of Rheumatology criteria for the diagnosis of giant cell
However, patients may present without classic systemic arteritis. Am J Ophthalmol. 2012; 154:617-619.
symptoms or with a variety of atypical, nonspecific constitu-
4. Hayreh SS, Podhajsky PA, Raman R, et al. Giant cell arteritis: valid-
tional symptoms, particularly early in the course of the disease.
ity and reliability of various diagnostic criteria. Am J Ophthalmol.
Further, occult GCA may present with ocular involvement in 1997; 123(3):285-296.
the absence of systemic signs or symptomatology in 21% of
patients.2 Given these atypical cases, a recent study estimates that 5. Parikh M, Miller NR, Lee AG, et al. Prevalence of a normal
the ACR criteria used in isolation may miss up to 25% of cases C-reactive protein with an elevated erythrocyte sedimentation
rate in biopsy-proven giant cell arteritis. Ophthalmology 2006;
of GCA.3 While studies have quoted the specificity of ESR and
113(10):1842-1845.
CRP in combination to be 97%,4 GCA may occur in the absence
of abnormally elevated inflammatory markers. Therefore, it 6. Imran TF, Helfgott S. Respiratory and otolaryngologic manifesta-
behooves the ophthalmologist both to identify expected ocular tions of giant cell arteritis. Clin Exp Rheumatol. 2015; 89(2):164-
signs of GCA and to recognize atypical systemic symptoms 170.
indicative of evaluation for temporal arteritis to properly direct 7. Zenone T, Puget M. Dry cough is a frequent manifestation of giant
patient management. In addition to large vessel involvement cell arteritis. Rheumatol Int. 2013; 33:2165-2168.
such as aortitis and aortic aneurysm, otolaryngeal and respira-
8. El-Dairi MA, Chang L, Bhatti T, et al. Diagnostic algorithm for
tory disorders such as intractable, nonproductive cough, trismus, patients with suspected giant cell arteritis. J Neuro-Ophthalmol.
and tongue infarction resulting from ischemia of affected tissues Epub ahead of print 2015 Mar 23.
may be the first presenting symptoms of GCA.6 A recent study
reported dry cough as a presenting symptom of GCA in 13.6%
2015 Subspecialty Day  |  Neuro-Ophthalmology Section III: Double Vision and Nystagmus 37

Section III: Double Vision and Nystagmus Made

Ridiculously Simple

“I see double, and my eyelid is in the the side of the CN VI nuclear lesion), often accompanied by CN
VII palsy as cranial nerve VII fibers curve around the sixth nerve
way.” nucleus. Brainstem lesions that affect the fascicle of the sixth
Paul H Phillips MD nerve may also damage the seventh nerve fascicle, tractus solitar-
ius, and the descending tract of the trigeminal nerve, causing an
ipsilateral abduction deficit, facial paresis, loss of taste over the
Final Diagnosis anterior 2/3 of the tongue, and facial hypoesthesia (Foville syn-
Right CN III palsy, CN VI palsy, and Horner syndrome from a drome). Lesions located in the ventral pons may affect the sixth
right cavernous sinus meningioma cranial nerve, seventh cranial nerve, and the corticospinal tract,
resulting in an ipsilateral abduction deficit, facial weakness, and
Cranial nerve VI innervates the lateral rectus muscle, and there- contralateral hemiplegia (Millard-Gubler syndrome). Lesions
fore a CN VI palsy is characterized by an abduction deficit that of the cerebellopontine angle may affect CN V (decreased facial
increases with gaze toward the affected eye and at distance.1 sensation), CN VI (abduction deficit), CN VII (facial weakness),
Injury may occur at multiple locations, including the nucleus, and CN VIII (decreased hearing and vestibular dysfunction).
fascicle, subarachnoid space, cavernous sinus, and orbit. Inflammation in the petrous bone may cause an ipsilateral CN
Multiple etiologies may cause CN VI dysfunction, including VI palsy and facial pain (Gradenigo syndrome). An abduction
ischemia, compression, inflammation (multiple sclerosis, sarcoid- deficit accompanied by proptosis suggests an orbital process
osis), infection, and trauma. An increase or decrease in intracra- affecting CN VI or the extraocular muscles (thyroid orbitopathy,
nial pressure may shift the brainstem and stretch CN VI, result- orbital pseudotumor).
ing in a unilateral or bilateral CN VI palsy. Thus, it is important The cavernous sinus contains cranial nerves III, IV, V1, V2,
to evaluate the disc for papilledema in patients that present with and VI, as well as the third-order, postganglionic ocular sympa-
CN VI palsy. thetic fibers. Any combination of ipsilateral dysfunction of these
Microvascular ischemia to the subarachnoid segment of the cranial nerves suggests cavernous sinus involvement.
nerve is a common cause of an isolated sixth-nerve palsy. The The third-order postganglionic sympathetic fibers ascend with
following characteristics support an ischemic etiology:2 the carotid artery into the cavernous sinus and join CN VI in the
posterior portion of the cavernous sinus.4,5 The fibers then join
• Age greater than 50 the ophthalmic branch of the trigeminal nerve and enter the orbit
• Arteriosclerotic risk factors such as hypertension, diabetes through the superior orbital fissure. Therefore, the combination
mellitus, hypercholesterolemia, tobacco use of a CN VI palsy and an ipsilateral postganglionic Horner syn-
• No history of cancer drome localizes the pathology to the posterior cavernous sinus.
• The abduction deficit remains isolated during follow-up Our patient presented with an isolated CN VI palsy that was
examination. consistent with an ischemic etiology. However, he subsequently
• The abduction deficit stabilizes after 1-2 weeks and developed an ipsilateral Horner syndrome as well as CN III pare-
improves in 3-4 months. sis, suggesting cavernous sinus pathology. Neuroimaging con-
If patients fulfill these criteria, many investigators will pre- firmed a cavernous sinus lesion consistent with a meningioma.
sume a microvascular etiology and not obtain neuroimaging at
onset. Associated risk factors such as diabetes and hypertension Teaching Points
should be evaluated, and the patient should be followed to con-
firm improvement of the abduction deficit within 3-4 months. 1. Ischemic cranial nerve palsies do not typically affect mul-
Progressive or unresolved palsies or additional neurological tiple cranial nerves simultaneously.
deficits mandate further neuroimaging. Murchison et al2 showed 2. Ischemic cranial nerve palsies should improve over 3-4
that following this algorithm is cost-effective and unlikely to miss months.
an alternative, treatable etiology. However, Chou et al3 showed 3. Unilateral dysfunction of multiple cranial nerves (III, IV,
that 4 of 19 patients (21%) with CN VI palsy that fulfilled these V1, V2, and VI) suggests cavernous sinus localization.
criteria had nonischemic etiologies, including neoplasm, brain- 4. The sympathetic fibers travel with CN VI in the posterior
stem infarct, multiple sclerosis, and pituitary apoplexy, and rec- cavernous sinus. Therefore, the combination of CN VI
ommend neuroimaging at presentation of all patients with CN palsy and Horner syndrome suggests cavernous sinus
VI palsy. localization.
Additional neurological deficits allow more refined local- 5. Controversy exists over whether to image an isolated CN
ization and mandate neuroimaging. Further diagnostic testing VI palsy in the vasculopathic older patient after the initial
should be considered, including lumbar puncture, chest imaging, visit, or to monitor closely.
and hematologic studies for etiologies such as syphilis, sarcoid-
osis, and collagen vascular disease.
A brainstem lesion affecting the sixth cranial nerve nucleus
will cause a gaze palsy (neither eye can rotate horizontally to
38 Section III: Double Vision and Nystagmus 2015 Subspecialty Day  |  Neuro-Ophthalmology

References “Things are blurry and jumpy when I

1. “The patient with diplopia.” In: Neuro-Ophthalmology: Basic and read.”
Clinical Science Course. San Francisco: American Academy of Oph-
thalmolgy 2014-2015: section 5, chapter 8, 212-221. Janet C Rucker MD
2. Murchison AP, Gilbert ME, Savino PJ. Neuroimaging and acute
ocular motor mononeuropathies: a prospective study. Arch Oph- Final Diagnosis
thalmol. 2011; 129(3):301-305.
Paraneoplastic cerebellar degeneration with downbeat nystag-
3. Chou KL, Galetta SL, Liu GT, et al. Acute ocular motor mononeu- mus and gait ataxia and positive paraneoplastic antibodies due
ropathies: prospective study of the roles of neuroimaging and clini- to recurrent ovarian cancer
cal assessment. J Neurol Sci. 2004; 219:35-39.
4. Gutman I, Levartovski S, Goldhammer Y, Tadmor R, Findler G.
Sixth nerve palsy and unilateral Horner’s syndrome. Ophthalmol-
Teaching Points
ogy 1986; 93:913-916.
Teaching Point 1: Nystagmus
5. Tsuda H, Ishikawa H, Kishiro M, Koga N, Kashima Y. Abducens Nystagmus is a spontaneous, repetitive movement of the eyes
nerve palsy and postganglionic Horner syndrome with or without
that is initiated by slow eye drifts away from desired eye posi-
severe headache. Intern Med. 2006; 45(14):851-855.
tion. It may be jerk (slow drifts followed by corrective fast move-
ments in the opposite direction) or pendular (to-and-fro slow
oscillations without fast corrective movements). Jerk nystagmus
is named by the direction of its fast movements (eg, “right beat-
“I see two golf club heads when I ing,” “up beating,” etc.). Both jerk and pendular nystagmus may
have horizontal, vertical, and/or torsional components. Oscillop-
putt.” sia, a subjective sensation of visual motion, is often experienced
Courtney E Francis MD by the patient with nystagmus and may be described as “jumping
vision” or simply as “blurred vision.”
Three main types of nystagmus are commonly seen in primary
Final Diagnosis
gaze with motion in the vertical direction. The first two are jerk
Thyroid eye disease with left inferior rectus restriction nystagmus: upbeat nystagmus (UBN) and downbeat nystagmus
(DBN). The third is acquired pendular nystagmus (APN). UBN
consists of slow drifts of the eyes downward with corrective fast
Teaching Points
movements upwards. It is, by definition, present in primary gaze
On further review, the patient had a remote history of Graves and is typically more prominent in upgaze. UBN is much less
disease, treated with methimazole and currently in remission. He common than DBN and APN and is most typically seen in mul-
was followed over time to ensure stability of his deviation for tiple sclerosis and Wernicke encephalopathy.
at least 6 months. He underwent left inferior rectus recession of DBN consists of slow drifts of the eyes upward with cor-
6 mm, with resolution of his symptoms. Small deviations may be rective fast movements downward. It is, by definition, present
managed conservatively with prism glasses. in primary gaze, but it may be of such low amplitude that it is
As alignment may change following surgery, orbital decom- invisible to the naked eye. It is much more prominent in lateral,
pressions should always be performed first if clinically indicated downward gaze (and is thus sometimes called “side-pocket nys-
and lid surgery should be reserved until after strabismus surgery. tagmus”). It is often absent or converted to upbeat nystagmus in
Care should be taken to avoid overcorrection in cases of inferior upgaze. A chin-down resting head position may be adopted by
rectus recession, which could lead to diplopia in downgaze. the patient to minimize oscillopsia. Strategies to optimize visual-
Additionally, some patients with restrictive strabismus from thy- ization of DBN in primary gaze include viewing the eye at the slit
roid eye disease can have late overcorrection after surgery. lamp with careful attention to scleral vessels for fast-downbeat
motion and assessing for DBN during dilated ophthalmoscopy.
DBN is idiopathic in a large percentage of cases, especially when
Selected Readings
it is an isolated finding. Other common causes include Chiari
1. Harrad R. Management of strabismus in thyroid eye disease. Eye I malformation, other cervicomedullary junction pathology,
2015; 29:234-237. and substance toxicities (eg, anti-convulsants, lithium, alcohol).
2. Peragallo JH, Velez FG, Demer JL, Pineles SL. Postoperative drift in DBN is also commonly seen in association with cerebellar dis-
patients with thyroid ophthalmopathy undergoing unilateral infe- ease from structural abnormalities on MRI (eg, stroke, tumor),
rior rectus muscle recession. Strabismus 2013; 21(1):23-28. genetic spinocerebellar degenerations, or with neurologically
active antibodies in the serum (eg, anti-GAD antibodies, para-
3. Volpe NJ, Mirza-George N, Binenbaum G. Surgical management of
vertical ocular misalignment in thyroid eye disease using an adjust-
neoplastic antibodies). The best-studied treatments for DBN are
able suture technique. J AAPOS. 2012; 16(6):518-522. the potassium channel blockers 4-aminopyridine (4-AP) and
3,4-diaminopyridine (3,4-DAP), in addition to chlorzoxazone
4. Bothun ED, Scheurer RA, Harrison AR, Lee MS. Update on thyroid and gabapentin.
eye disease and management. Clin Ophthalmol. 2009; 3:543-551.
APN consists of slow pendular oscillations of the eyes without
5. Chen VM, Dagi LR. Ocular misalignment in Graves disease may fast corrective movements. It is commonly seen in two scenarios:
mimic that of superior oblique palsy. J Neuroophthalmol. 2008; multiple sclerosis and oculopalatal tremor (OPT). In OPT, it
28(4):302-304. accompanies tremor of the palate and is typically seen weeks to
months following a stroke in the brainstem. MRI in OPT reveals
2015 Subspecialty Day  |  Neuro-Ophthalmology Section III: Double Vision and Nystagmus 39

increased T2 signal in and hypertrophy of the inferior olives in signs or symptoms, or history of onset after trauma are
the medulla. APN in MS often has a horizontal or elliptical tra- important. In this setting, neurologic workup with imag-
jectory. In OPT, it is often vertical. The two most effective treat- ing and/or lumbar puncture may be helpful.
ments for APN are gabapentin and memantine.

Teaching Point 2: Paraneoplastic syndromes Selected Readings

Paraneoplastic syndromes cause cancer-related, immune- 1. Liu GT, Volpe NJ, Galetta SL. Eye movement disorders: third,
mediated, acute to subacute decline in nervous system function fourth, and sixth nerve palsies and other causes of diplopia and
remote from a cancer site. They are most commonly associated ocular misalignment. In: Neuro-ophthalmology: Diagnosis and
with small-cell cancers such as lung cancer but are also often Management, 2nd ed. New York: Saunders Elsevier; 2010:491-550.
seen with ovarian and breast carcinoma and testicular germ cell 2. Kline LB, Foroozan R. Supranuclear and internuclear gaze path-
tumors. Typical paraneoplastic syndromes that involve vision ways. In: Neuro-Ophthalmology Review Manual, 7th ed. Thoro-
include optic neuropathy, retinopathy, cerebellar degeneration fare, NJ: SLACK Inc.; 2013:45-72.
with downbeat nystagmus, and opsoclonus. Paraneoplastic 3. Jacobson DJ. Divergence insufficiency revisited: natural history of
antibodies are commonly present in serum. It is very important idiopathic cases and neurologic associations. Arch Ophthalmol.
to be aware that the cancer is often occult and undiagnosed at 2000; 118:1237-1241.
time of onset of the visual or neurological symptoms, and inten-
4. Chaudhuri Z, Demer JL. Sagging eye syndrome: connective tissue
sive, exhaustive search for an underlying malignancy is critical.
involution as a cause of horizontal and vertical strabismus in older
If no malignancy is identified and a paraneoplastic syndrome is patients. JAMA Ophthalmol. 2013; 131(5):619-625.
strongly suspect, periodic surveillance for malignancy should be
performed annually for at least 5 years. 5. Mittelman D. Age-related distance esotropia. J AAPOS. 2006;
10(3):212-213.

Selected Readings
1. Mehta AR, Kennard C. The pharmacological treatment of acquired
nystagmus. Pract Neurol. 2012; 12:147-153.
“I see double when I get tired.”
2. Thurtell MJ, Leigh RJ. Nystagmus and saccadic intrusions. Handb
Clin Neurol. 2011; 102:333-378. Marc J Dinkin MD
3. Rucker JC. An update on acquired nystagmus. Semin Ophthalmol.
2008; 23:91-97. Final Diagnosis
4. Ko MW, Dalmau J, Galetta SL. Neuro-ophthalmologic manifesta- Myasthenia gravis
tions of paraneoplastic syndromes. J Neuroophthalmol. 2008;
28:58-68.
Teaching Points
1. Congenital strabismus may become symptomatic when the
patient is fatigued, such as at the end of the day.
2. Myasthenia can mimic any eye movement pattern.
“Words run together on the TV.” 3. Other strabismus patterns that suggest a congenital origin
Kimberly M Winges MD include an intermittent V-pattern esotropia, pure inferior
oblique overaction, a limitation of elevation of an eye
when adducted (suggestive of a Brown syndrome), or
Final Diagnosis limitation of abduction of an eye (suggestive of a Duane
Divergence insufficiency, secondary to spinocerebellar ataxia syndrome).
4. Specific exam features that help confirm a congenital ori-
gin are:
Teaching Points • High fusional amplitude: When increasing prism is
1. Divergence insufficiency (DI) is defined as a comitant eso- added in the vertical plane, for example, above and
phoria or esotropia worse at distance than near (or absent beyond what is needed to remove the phoria, the
at near), with full ductions and no evidence of cranial patient with congenital strabismus will often continue
nerve palsy. to be able to fuse the two images, without diplopia,
2. DI can be secondary to neurologic causes, or it can be pri- over a large number of additional prism diopters. In
mary (idiopathic). A poorly defined divergence center in contrast, the myasthenic patient, who has not had a
the caudal pons is hypothesized to be responsible for neu- lifetime to cortically adapt to the strabismus, will typi-
rologic divergence paralysis. More recently, involutional cally not have a high fusional amplitude.
changes within the orbital connective tissue and extraocu- • The finding of a compensatory head turn or tilt on old
lar muscles have been recognized as non-neurologic causes photos
of distance esotropia in older individuals. Most patients • In the case of a limitation of abduction, the presence of
with DI in isolation do not develop future neurologic dis- retraction on adduction is highly suggestive of Duane’s
ease. syndrome.1
3. The main differential diagnosis of DI is bilateral CN VI • In the case of limited elevation on adduction, a positive
palsy, and careful attention to signs of increased intracra- forced duction test suggests a restriction of the superior
nial pressure, other cranial nerve involvement, neurologic oblique tendon consistent with Brown syndrome.
40 Section III: Double Vision and Nystagmus 2015 Subspecialty Day  |  Neuro-Ophthalmology

5. Fatigable ptosis on sustained upgaze suggests ocular myas- 3. Nagia L, Lemos J, Abusamra K, Cornblath WT, Eggenberger ER.
thenia but may also be present in up to 38% of patients Prognosis of ocular myasthenia gravis: retrospective multicenter
who do not have the disease.2 analysis. Ophthalmology. Epub ahead of print 2015 Apr 16. doi:
6. The onset of a new fatigable ptosis over a background of 10.1016/j.ophtha.2015.03.010.
fatigable diplopia is highly suggestive of myasthenia gra- 4. Gorelick PB, Rosenberg M, Pagano RJ. Enhanced ptosis in myas-
vis, making decompensation of a congenital strabismus as thenia gravis. Arch Neurol. 1981; 38(8):531.
the cause of the diplopia much less likely. However, some 5. Ishikawa H, Wakakura M, Ishikawa S. Enhanced ptosis in Fisher’s
patients presenting with a decompensation of a congenital syndrome after Epstein-Barr virus infection. J Clin Neuroophthal-
strabismus may also have ptosis from other causes, most mol. 1990; 10(3):197-200.
often mechanical. And in fact, such a lid may also be more
6. Cogan DG. Myasthenia gravis: a review of the disease and a
difficult to keep up when the patient is tired. Thus, the
description of lid twitch as a characteristic sign. Arch Ophthalmol.
combination of ptosis and fatigable diplopia should not be
1965; 74:217-221.
looked at as pathognomonic for myasthenia.
7. Lack of systemic fatigable weakness is consistent with a 7. Van Stavern GP, Bhatt A, Haviland J, Black EH. A prospective
diagnosis of ocular myasthenia, although in a recent study, study assessing the utility of Cogan’s lid twitch sign in patients
20.9% of patients will convert to generalized myasthenia with isolated unilateral or bilateral ptosis. J Neurol Sci. 2007;
256(1Y2):84-85.
over the next two years.3
8. The presence of enhanced ptosis (curtaining) is not spe- 8. Osserman KE, Kaplan LI. Rapid diagnostic test for myasthenia
cific to ocular myasthenia, as it reveals a weakness of the gravis: increased muscle strength, without fasciculations, after intra-
apparently uninvolved levator palpebrae muscle which is venous administration of edrophonium (Tensilon) chloride. J Am
brought out by passive lifting of the ptotic lid,4 although Med Assoc. 1952; 150(4):265Y268.
it has been described in other conditions as well.5 This is 9. Odel JG, Winterkorn JM, Behrens MM. The sleep test for myasthe-
an example of Herring’s Law: that the force put into one nia gravis: a safe alternative to Tensilon. J Clin Neuroophthalmol.
extraocular muscle is equal in both eyes. Cogan lid twitch 1991; 11(4):288.
is another finding classic for ocular myasthenia6 but is not 10. Benatar M. A systematic review of diagnostic studies in myasthenia
ubiquitously observed.7 gravis. Neuromuscul Disord. 2006; 16:459-467.
9. The Tensilon test has a high specificity for myasthenia but
may cause syncope or, rarely, cardiac arrhythmias.8 11. Padua L, Stalberg E, LoMonaco M, et al. SFEMG in ocular myas-
thenia gravis diagnosis. Clin Neurophysiol. 2000; 111:1203-1207.
10. The rest test is a sensitive and specific assessment for
ocular myasthenia but requires rigorous documentation 12. Lee JJ, Koh KM, Kim US. The anti-acetylcholine receptor antibody
before and after a 20-minute session of eye closure.9 test in suspected ocular myasthenia gravis. J Ophthalmol. 2014;
11. A decrement on repetitive nerve stimulation (RNS) test- 2014:689792.
ing is highly specific for myasthenia,10 but the test has a 13. Roh HS, Lee SY, Yoon JS. Comparison of clinical manifestations
sensitivity as low as 24%2 so that a lack of decrement does between patients with ocular myasthenia gravis and generalized
not rule out myasthenia. Single fiber EMG may reveal myasthenia gravis. Korean J Ophthalmol. 2011; 25(1):1-7.
increased jitter in cases of OMG, and has a higher sensitiv-
14. Tung CI, Chao D, Al-zubidi N, et al. Invasive thymoma in ocular
ity (90%-95%) than RNS,11 but it requires arduous and myasthenia gravis: diagnostic and prognostic implications. J Neur-
time-consuming testing and is only performed by select oophthalmol. 2013; 33(3):307-308.
experts.
12. Acetylcholine receptor antibodies may be elevated in pure 15. Son SM, Lee YM, Kim SW, Lee OJ. Localized thymic amyloidosis
presenting with myasthenia gravis: case report. J Korean Med Sci.
ocular myasthenia, but sensitivity is low, ranging from
2014; 29(1):145-148.
14.1%12 to 50%.13
13. Some patients with ocular myasthenia harbor a thoracic 16. Chapman KO, Beneck DM, Dinkin MJ. Ocular myasthenia gravis
thymoma, and in rare cases the tumor may be malignant,14 associated with thymic amyloidosis. J Neuroophthalmol. Epub
or even more rarely, as in this case, be composed of amy- ahead of print 2015 Mar 27.
loid.15,16 17. Anthony SA, Thurtell MJ, Leigh RJ. Miller Fisher syndrome
14. Other entities that may mimic ocular myasthenia because mimicking ocular myasthenia gravis. Optom Vis Sci. 2012;
of a diurnal variability include Miller Fisher syndrome17 89(12):e118-123.
and silent sinus syndrome.18 The latter is associated with 18. Coombs PG, Mitchell J, Lelli G, Dinkin MJ. A case of silent sinus
hypoglobus, or inferior positioning of the globe, due to syndrome caused by a dacryocystorhinostomy presenting as myas-
an inferior bowing of the orbital flow into a low pressure thenia gravis. North American Neuro-ophthalmology Society.
maxillary sinus, thus producing a vertical diplopia.19 Such 2014; Abstract 91.
“sinking” may worsen later in the day due to the effects of
19. Saffra N, Rakhamimov A, Saint-Louis LA, Wolintz RJ. Acute dip-
gravity, thus mimicking the fatigability of myasthenia. lopia as the presenting sign of silent sinus syndrome. Ophthal Plast
Reconstr Surg. 2013; 29(5):e130Y-131.
References
1. Hotchkiss MG, Miller NR, Clark AW, Green WR. Bilateral
Duane’s retraction syndrome: a clinical-pathologic case report.
Arch Ophthalmol. 1980; 98(5):870-874.
2. Mittal MK, Barohn RJ, Pasnoor M, et al. Ocular myasthenia gravis
in an academic neuro-ophthalmology clinic: clinical features and
therapeutic response. J Clin Neuromuscul Dis. 2011; 13(1):46-52.
2015 Subspecialty Day  |  Neuro-Ophthalmology Section III: Double Vision and Nystagmus 41

“I see double after my cataract

surgery.”
Stacy L Pineles MD

Final Diagnosis
The presence of diplopia combined with a history of childhood
amblyopia and strabismus raises the suspicion for fixation switch
diplopia.

Teaching Points
Fixation switch diplopia should be suspected in patients with a
history of childhood strabismus or amblyopia who become dip-
lopic after an intervention forces them to switch fixation to their
previously amblyopic eye. Treatment typically involves restora-
tion of fixation with the previously dominant eye using optical or
surgical means. Prisms can also be used as a short-term solution
if necessary in cases where there is coexistent strabismus.
42 Section IV: Test Interpretation 2015 Subspecialty Day  |  Neuro-Ophthalmology

Section IV: Test Interpretation Made

Ridiculously Simple

What Do I Do With This Visual Field? nerve, chiasmal, and optic tract compression, and interpreting
these defects can be challenging. Lesions that affect the anterior
Gregory P Van Stavern MD angle of the chiasm and the distal optic nerve produce a junc-
tional scotoma, a distinct syndrome characterized by an optic
Final Diagnosis nerve-related defect in the eye ipsilateral to the tumor, and a
superotemporal defect in the eye contralateral to the mass. The
Suprasellar meningioma compressing the intracranial optic nerve contralateral temporal visual field defect is usually superotempo-
and optic chiasm, causing a junctional scotoma ral (reflecting the inferonasal crossing fibers) but may be a com-
plete temporal hemianopia.
Teaching Point 1 The origin of the superotemporal, contralateral visual field
defect is of both historical and clinical interest. Wilbrand pro-
The visual field is one of the most important tools in the oph- posed that crossed fibers originating from ganglion cells inferior
thalmologist’s armamentarium, as it allows precise localization and nasal to the fovea in the contralateral eye extend anteriorly
of pathology within the afferent visual pathways. The retinal (< 2 mm) into the involved optic nerve and are thus subject to
nerve fiber layer is highly topographically organized, and that compression. This anatomic configuration is known as “Wil-
topography is preserved throughout the visual pathway: a lesion brand’s knee.” Although some believe that Wilbrand’s knee is
anywhere from the retina to the primary visual cortex will cause simply a pathologic artifact rather than a true anatomic struc-
predictable visual field defects, which can then narrow the dif- ture, its clinical relevance remains unquestioned, and the finding
ferential diagnosis of the patient’s visual complaints and guide of a “junctional” visual field defect provides strong evidence of
diagnostic workup. a lesion at the anterior angle of the chiasm, mandating neuro­
Visual field testing by perimetry should be performed in imaging.
any patient with unexplained visual loss and is a key element Neuroimaging is indicated for all patients suspected of hav-
in monitoring patients with known disease such as glaucoma ing a compressive optic neuropathy. The ideal modality is MRI
and idiopathic intracranial hypertension. All perimetry methods of the brain, with and without gadolinium, with fat-saturated
are prone to inter-test variability, interoperator variability, and orbital views. This offers superb views of the globe, optic nerve
performance failures, and should be interpreted in the context of head, optic nerve sheath, extraocular muscles, and orbital apex.
the entire examination and the results of confrontation testing. It is also superior to CT for the evaluation of the intracanalicular
Indeed, careful confrontation perimetry can be a great ally, as a and intracranial optic nerve, the pituitary fossa, and the cavern-
completely normal confrontation field (particularly when tested ous sinuses.
using a small red target) is inconsistent with extensive visual field Treatment is dependent upon the specific type of tumor and
loss seen on automated or kinetic perimetry, and should raise the location, size, and degree of optic nerve dysfunction. The
suspicion of artifact or performance issues. prognosis for visual outcome is related in part to duration of
Patterns of visual field loss are highly localizing, so accurate compression, as well as retinal ganglion cell and retinal nerve
interpretation relies upon basic knowledge of visual pathway fiber layer integrity. Patients with severe optic atrophy at pre-
neuroanatomy. In particular, the vertical meridian should be sentation (indicating loss of neurons and axons) have a worse
carefully examined. The optic chiasm is the anatomic substrate prognosis for recovery, although some of these patients may have
for the vertical meridian, and any visual field defect that respects partial improvement after decompression.
the vertical midline raises concern for a chiasmal or retrochias-
mal lesion. Automated static perimetry is probability-based, and
the defects seen are not always as clean or “pretty” as those seen Teaching Point 2
with kinetic perimetry, so it is important to review the field care- The diagnosis of “previous NAION” should be used with cau-
fully to see if there is any portion of the defect that lines up along tion unless the patient had documented optic nerve swelling
the vertical midline, even if there is some apparent crossover on at presentation and a history and subsequent clinical course
the probability plots. When interpreting any visual field, it is compatible with that diagnosis. It is important to remember that
helpful to ask the following questions: NAION is ultimately a clinical diagnosis, supported by features
1. Is the test reliable? such as acute onset, optic disc swelling, presence of a small,
2. Is the test normal? crowded optic disc, and subsequent stabilization with spontane-
3. Does the visual field defect involve one eye or both eyes? ous resolution of optic disc edema. There are several “red flags”
4. If both eyes, does the defect respect the vertical meridian? in the history and examination that suggest a diagnosis other
5. If the defects respects the vertical meridian, is it bitemporal than a previous episode of NAION:
or junctional (optic chiasm) or homonymous (retrochias- 1. No documentation of a swollen optic disc
mal)? 2. Gradual rather than acute onset
Sellar and suprasellar tumors may cause intracranial optic 3. Lack of a small, crowded optic disc (cup-to-disc < 0.2)
nerve as well as chiasmal compression. Therefore, with such 4. Visual field defect that respects the vertical meridian
tumors it is not rare to see visual field defects that reflect optic 5. Progression of vision loss in the absence of disc swelling
2015 Subspecialty Day  |  Neuro-Ophthalmology Section IV: Test Interpretation 43

The ophthalmologist should have a high index of suspicion 2.  Retinal nerve fiber layer and macular OCT (segmentation)
for a compressive optic neuropathy in such patients, for the fol- When interpreting the OCT, it is important to review not only
lowing reasons: the retinal nerve fiber layer but the macular thickness maps and
1. Early detection of a mass may result in better prognosis for the individual cross-sectional images. The thickness of the retinal
vision and survival (if neoplastic). nerve fiber layer is influenced by not only the integrity of the
2. In many cases, the mass lesion may pose a risk to the unaf- axons of the ganglion cells but glial cells and blood vessels.2 The
fected eye. macular thickness map and retinal segmentation can provide
3. Visual loss may recover once the compressive lesion is valuable information regarding the anatomical / structural status
treated. of the different layers of the retina. Certain disease processes
have a predilection for particular layers of the retina. For exam-
Indeed, compressive optic neuropathies are among the ple, retinal artery occlusion causes thinning of the inner layers of
most treatable forms of optic nerve dysfunction, and dramatic the retina, and acute macular neuroretinopathy (AMNR) affects
recovery may occur with decompression of the visual pathways. the outer retinal layers.3 Furthermore, it has been shown that
Therefore, early detection is critical, as the visual loss may be macular OCT findings can aid in differentiating postacute retinal
reversible. The presence of a junctional scotoma in this case artery occlusion from nonacute optic neuropathies. Ghazi et al
strongly indicated that a compressive lesion was present. performed a retrospective OCT study of 17 eyes with postacute
retinal artery occlusion and 32 eyes with nonacute optic neuro­
Selected Readings pathy.4 They found 3 main features that distinguished postacute
retinal artery occlusion from nonacute optic neuropathy:
1. Volpe NJ. Compressive and infiltrative optic neuropathies. In:
Walsh and Hoyt’s Clinical Neuro-Ophthalmology, 6th ed. Philadel- 1. Complete inner retinal atrophy with loss of the normal
phia: Lippincott Williams and Wilkins; 2005:385-430. stratification of the inner retinal layers
2. Loss of the normal foveal depression
2. Foroozan R. Chiasmal syndromes. Curr Opin Ophthalmol. 2003;
14(6):325-331.
3. Marked thinning of the involved retina compared to non-
acute optic neuropathy
3. Horton J. Wilbrand’s knee of the primate optic chiasm is an artefact
of monocular enucleation. Trans Am Ophthalmol Soc. 1997; 95:1- Furthermore, Dolan et al demonstrated that macular thinning
31. was more profound in eyes with retinal artery occlusion than
in eyes with nonarteritic anterior ischemic optic neuropathy.5
4. Lee AG, Chau FY, Golnik KC, et al. The diagnostic yield for the
evaluation of isolated unexplained optic atrophy. Ophthalmology
Improved resolution with currently available spectral domain
2005;112:757-759. OCT allows for the segmentation of the various layers of the ret-
ina, thereby distinguishing localized retinal nerve fiber layer and
ganglion cell layer thinning associated with optic neuropathies
from the more diffuse inner retinal layer thinning associated with
retinal artery occlusion.
Should I Trust My Exam, or the OCT?
M Tariq Bhatti MD References
1. Newman NJ. Optic disc pallor: a false localizing sign. Surv Oph-
Final Diagnosis thalmol. 1993; 37(4):273-282.

Branch retinal artery occlusion with secondary optic nerve 2. Kardon RH. Role of the macular optical coherence tomogra-
­atrophy. phy scan in neuro-ophthalmology. J Neuroophthalmol. 2011;
31(4):353-361.
3. Fawzi AA, Pappuru RR, Sarraf D, et al. Acute macular neuro-
Teaching Points retinopathy: long-term insights revealed by multimodal imaging.
Retina 2012; 32(8):1500-1513.
1.  Primary optic nerve pallor vs. secondary optic nerve pallor
Optic nerve pallor can be a false localizing sign because not all 4. Ghazi NG, Tilton EP, Patel B, Knape RM, Newman SA. Compari-
son of macular optical coherence tomography findings between
cases of optic nerve pallor are due to primary optic nerve pathol-
postacute retinal artery occlusion and nonacute optic neuropathy.
ogy.1 Retinal dystrophies (in particular cone dystrophies), retinal
Retina 2010; 30(4):578-585.
degenerations (ie, retinitis pigmentosa), and retinal artery occlu-
sions can all result in secondary optic nerve pallor. In some cases, 5. Dotan G, Goldenberg D, Kesler A, Naftaliev E, Loewenstein A,
especially if nonacute, it can be clinically challenging to differ- Goldstein M. The use of spectral-domain optical coherence tomog-
entiate primary optic nerve pallor from secondary optic nerve raphy for differentiating long-standing central retinal artery occlu-
sion and nonarteritic anterior ischemic optic neuropathy. Ophthal-
pallor. Prior to the development of OCT, intravenous fluorescein
mic Surg Lasers Imaging Retina. 2014; 45(1):38-44.
angiography and electrophysiology, in addition to the clinical
examination, were required. The addition of OCT to the arma-
mentarium of paraclinical tests allows for quick identification of
retinal pathology that otherwise might be below the threshold of
funduscopic examination.2
44 Section IV: Test Interpretation 2015 Subspecialty Day  |  Neuro-Ophthalmology

“I can’t get cocaine drops in my through the arachnoid villi.3 Venous hypertension is common in
CVST patients, who often manifest symptoms and signs of raised
office!” intracranial pressure including headaches, papilledema, and
Heather E Moss MD PhD altered mental status.3 Additional features on examination may
include cranial nerve palsies, focal neurological deficits, seizures,
encephalopathy, and coma.2
Final Diagnosis Radiographic features of CSVT depend largely on the imag-
Small cell lung cancer of the right lung apex causing right Horner ing modality utilized. Noncontrast computed tomography (CT)
syndrome imaging of the head may show venous hemorrhage or infarc-
tion.2 Occasionally hyperdense signal changes within the affected
sinus may be identified.2 With contrast administration and CT
Teaching Points venography, a filling defect in a sinus may be seen. MRI may
1. Physical exam findings are free and quick tests that guide show venous thrombosis that is isointense on T1- and hypoin-
the differential diagnosis of ptosis and anisocoria and can tense on T2-weighted imaging, thus mimicking a “flow void”;
be diagnostic of Horner syndrome. subacute venous blot may become hyperintense on T1-weighted
2. Eye drop testing is helpful to confirm an equivocal diagno- imaging. Notably, 2-D time-of-flight MR-venography is rou-
sis of Horner syndrome or in a patient where neuroimag- tinely performed in suspected cases, albeit contrast MR venog-
ing evaluation poses risks. raphy is generally more sensitive in detecting CVST. Although
3. The most important reason to diagnose Horner syndrome digital subtraction angiography has historically been the gold
is to prompt workup for treatable etiologies: standard, the relative lack of experienced angiographers and the
a. If recent medical history provides an etiology, no addi- invasive nature of the examination has led to a dramatic decline
tional testing may be needed. in its use.2 Despite major improvement in MRI techniques over
b. Imaging of the sympathetic chain will screen for lesions the past decade, misinterpretation of brain MRI resulting in
causing Horner syndrome. delayed diagnosis of CVST remains common.3 Imaging of the
intracranial venous system with MR-venography is not system-
atically requested by many clinicians evaluating patients with a
Selected Readings syndrome of isolated raised intracranial pressure, and radiolo-
1. Almog Y, Gepstein R, Kesler A. Diagnostic value of imaging in gists are often asked to “rule-out CVST” on an isolated brain
Horner syndrome in adults. J Neuroophthalmol. 2010; 30:7-11. MRI.3 This may lead to false negative results. For the general
2. Davagnanam I, Fraser CL, Miszkiel K, Daniel CS, Plant GT. Adult ophthalmologist, CT or MR venography techniques are useful in
Horner’s syndrome: a combined clinical, pharmacological, and the evaluation of patients with suspected raised intracranial pres-
imaging algorithm. Eye 2013; 27:291-298. sure, particularly for those with atypical clinical features. In the
case presented, the patient was obese, but her weight loss, under-
3. Trobe J. The evaluation of Horner syndrome. J Neuroophthalmol.
lying comorbidities, and seizures argued against the diagnosis of
2010; 30:1-2.
idiopathic intracranial hypertension and in favor of CVST.
The mainstay of treatment for CVST is anticoagulation, even
in the setting of hemorrhagic venous infarction. The natural
history of CVST is highly variable, with some patients having
“The MRI is abnormal; now what?” minimal or no symptoms and an uneventful recovery (~65%),
whereas others have a fulminant course culminating in extensive
Fiona E Costello MD venous infarction, blindness, dependency, or death (~20%).2
Interventional neuroradiologists can perform catheter-directed
Diagnosis thrombolysis by using targeted thrombolytics in the affected
sinuses. As expected, hemorrhagic venous infarcts and coexisting
Repeat review of the MR-venogram reveals the diagnosis of cere- malignancy correlate with poor outcome.2 Deep cerebral venous
bral venous sinus thrombosis as the cause of the patient’s seizures thrombosis also has a negative impact on prognosis due to what
and manifestations of raised intracranial pressure. is often bilateral involvement of the thalami.2 Dural arteriovenous
fistula and increased cerebrospinal fluid pressure can also lead to
Teaching Points long-term complications after cerebral venous thrombosis.2
Cerebral venous sinus thrombosis (CVST) is a form of stroke
whereby thrombosis occurs in the cerebral venous sinuses or References
veins.1 The incidence of CVST has been estimated at 3 to 5 cases 1. Amoozegar F, Ronksley PE, Sauve R, Menon B. Hormonal contra-
per million population per year, representing 0.5%- 1% of all ceptives and cerebral venous thrombosis risk: a systematic review
strokes.1 This condition tends to affect individuals aged less than and meta-analysis. Front Neurol. Published online 2015 Feb 2. doi:
50 years, and is 3 times more common in women than men.1 10.3389/fneur.2015.00007.
CVST frequently affects patients with underlying risk factors for
2. Di Muzio B, Gaillard F, et al. Cerebral venous thrombosis. Radio-
venous clot formation, including pregnancy, oral contraceptive paedia. N.d. Available at: http://radiopaedia.org/articles/cerebral-
pill use, systemic disease (eg, Crohn disease), infection (eg, mas- venous-thrombosis.
toid sinus disease), and malignancy.1-2
The clinical features of CVST may vary and evolve over time. 3. Ridha MA, Saindane AM, Bruce BB, et al. MRI findings of elevated
intracranial pressure in cerebral venous thrombosis versus idio-
Thrombosis or stenosis of cerebral venous sinuses results in
pathic intracranial hypertension with transverse sinus stenosis.
intracranial venous hypertension, which causes raised intracra- Neuroophthalmol. 2013; 37(1):1-6.
nial pressure by reducing passive cerebrospinal fluid resorption
2015 Subspecialty Day  |  Neuro-Ophthalmology Section IV: Test Interpretation 45

Everyone’s ESR Is High: Who Needs ical scenarios the specificity of a pathology-supported diagnosis
carries significant weight when the risks of prolonged steroid
a Biopsy? treatment are considered or encountered months later. A positive
Todd Alan Goodglick MD biopsy heightens attention to atypical or vague symptoms that
might have been ignored otherwise. The sensitivity of a temporal
artery biopsy, even when done in a standardized manner, is not
Final Diagnosis known as this number would also depend on standardizing a
Giant cell arteritis “pretest” population of patients with respect to suspicious symp-
toms and signs of the disease and an alternative gold standard for
the diagnosis. Without a better understanding of the pathogen-
Teaching Points esis of the disease this is not presently available. What is known
The diagnosis of giant cell arteritis (GCA) is straightforward in is that a specific size of biopsy specimen would be expected to
textbook cases where an elderly patient presents with temporal increase the sensitivity as skip lesions of foci of inflammation are
headache, scalp tenderness, classic jaw claudication (ie, cre- known to commonly occur. A length of a fixed biopsy > 1.5–2.0
scendo pain with chewing), and sudden loss of vision. However, cm has often been found to be associated with a higher positive
this diagnosis comes up far more frequently in the differential rate.
diagnosis for variations of these symptoms such as atypical head- There is a trend to diminish the utility of a temporal artery
ache, transient vision loss, double vision, or even the incidental biopsy due to the perception of a (probably overestimated) false
finding of an elevated sedimentation rate, platelet count, or negative rate.3 When properly done the false negative rate is,
C-reactive protein. This of course is particularly true when try- although unknown, believed to be low. A properly done biopsy
ing to make the diagnosis early to prevent the dreaded outcome involves obtaining a piece of artery, localized to the pain and
of permanent vision loss (incidence in GCA is 15%-30% of about 2 cm long given the possibility of skip lesions of inflamma-
cases). Eye doctors in particular need to maintain a high level of tory foci, which are known to occur frequently. Positive results
vigilance, as 20% of GCA patients present with only ophthalmo- would include the presence of a mononuclear infiltrate through-
logic complaints. out the wall of the muscular artery with characteristic but not
What is known is that GCA is an inflammatory vasculopathy mandatory giant cells and destruction of the internal elastic
involving medium and large arteries including branches of the lamina.
external carotids; ophthalmic, vertebral, and distal subclavian The presence of giant cells distinguishes GCA from non-giant
arteries; and thoracic aorta. There is an association with the dis- cell arteritides such as ANCA-positive vasculitis. Findings sugges-
ease polymyalgia rheumatica (PMR), which may pre- or postdate tive of atherosclerotic changes would not be considered positive.
the diagnosis of GCA and cause diffuse myalgias of the neck A biopsy of the superficial temporal artery is a straightfor-
and proximal extremities. About 50% of GCA patients will also ward outpatient procedure. The notion of a substantial false
attain a diagnosis of PMR at some point. PMR is 10 times as negative rate for temporal artery biopsies thus needs to be inter-
common as GCA, so PMR cannot be a highly specific risk fac- preted with caution but (somewhat) limits the utility of such a
tor for GCA even though a diagnosis of PMR often raises such result in ruling out the disease. A negative result in the presence
a concern. Similarly, ethnicity can be used only as a relative risk of classic symptoms might be regarded as a false negative and
factor, with the incidence in northern European whites twice as treatment continued, but otherwise a negative result can be used
high as those of southern European descent and 20 times that as a strong indicator against this diagnosis and a positive result
in patients of Asian and African descent.1 Because of the lack of makes the diagnosis unquestionable. A negative result suggests
knowledge about the etiology of the disease or until there are more than an elimination of a diagnosis of GCA, and itself has a
sensitive and specific biomarkers for disease activity, there will differential diagnosis.4
always be ambiguous cases. Part of the confusion about the diagnosis has arisen from the
The sensitivity of an elevated age-corrected sed rate (Wester- American College of Rheumatology diagnostic criteria for this
gren erythrocyte sedimentation rate (ESR) (age + 10 for men disease, in which 3 of 5 criteria need to be met for a diagnosis,
or age divided by 2 for women) in biopsy-confirmed GCA has only 1 of which is a positive biopsy. These criteria, however,
been estimated at 84%; and that for elevated C-reactive protein were created in order to differentiate the various vasculitides and
(CRP), 86%. The specificity of these values was low, measuring are of limited use in typical clinical diagnostic situations.3
30% for either. Furthermore, only 4% of biopsy-proven patients Simultaneous biopsy of both sides is not necessarily recom-
had a normal value for both. mended routinely as it is thought to increase the yield of a posi-
Put another way, a high ESR is a nonspecific indicator of tive diagnosis by 1%-4%. Biopsy of the second side should be
inflammation, and a normal ESR is reported in up to 20% of considered if there is a significant degree of suspicion for the
cases of GCA. The combination of elevated ESR and CRP has a disease despite an initial negative biopsy, given the usefulness of
sensitivity of 98%. The odds ratio predicting a positive temporal a tissue diagnosis. Frozen section of the artery has an 18% false
artery biopsy was 5 times for an elevated CRP, 4 times greater negative rate and cannot be relied upon.5
for thrombocytosis, and 1.5 times greater for an elevated ESR.2 The approach should be “treat and then biopsy,” using
However, these numbers (and all such statistics in this disease) response to steroids as a significant and highly typical clinical
are truly applicable only in a population with a proven diagnosis occurrence. The histologic findings are thought to persist for at
as opposed to the population encountered in clinical settings least 2-3 weeks after initiation of steroids, with evidence that
with variably suspicious symptoms. Clinicians are thus justifiably changes of healed arteritis may be found up to 1 year later.
confused when it comes to ruling in or out a diagnosis of GCA. In conclusion, the difficulties in making the diagnosis of GCA
In all cases the diagnosis of GCA is best made, when possible, stem from our present lack of understanding of the etiology and
histologically rather than clinically. Even in the most typical clin- the lack of specific markers of that process. There are presently
no imaging modalities (ultrasound, MRI, PET) that have reli-
46 Section IV: Test Interpretation 2015 Subspecialty Day  |  Neuro-Ophthalmology

able diagnostic sensitivity or specificity.1 What remains is a high

level of suspicion and the temporal artery biopsy, including in
situations where systemic symptoms are being evaluated such as
fever of unknown origin, generalized myalgias, night sweats, and
weight loss, all primarily aimed at trying to prevent the devastat-
ing loss of vision that this disease can cause.

References
1. Weyand CM, Goronzy JJ. Giant cell arteritis and polymyalgia rheu-
matica. N Engl J Med. 2014; 371(17):50-57.
2. Walvick MD. Giant cell arteritis: laboratory predictors of a positive
temporal artery biopsy. Ophthalmology 2011; 118:1201-1204.
3. Danesh-Meyer H. Temporal artery biopsy: skip it at your patient’s
peril [editorial]. Am J Ophthalmol. 2012; 154 (4):617-619.
4. Roth AM, Milsow L, Keltner JL. The ultimate diagnoses of patients
undergoing temporal artery biopsies. Arch Ophthalmol. 1984;
102:901-903.
5. Taylor-Gjevre R, Vo M, Shukla D, Resch L. Temporal artery
biopsy for giant cell arteritis. J Rheumatol. 2005; 32:1279-1282.
2015 Subspecialty Day  |  Neuro-Ophthalmology  47

Financial Disclosure

Transparency through disclosure of relationships with compa- Financial Relationship Disclosure

nies is one step in the Academy’s process of ensuring that all its
For purposes of this disclosure, a known financial relationship
educational activities are fair, balanced, and not commercially
is defined as any financial gain or expectancy of financial gain
biased. The Academy’s Board of Trustees supports the position
brought to the Contributor or the Contributor’s immediate fam-
that having a financial relationship should not restrict expert
ily (defined as spouse, domestic partner, parent, child or spouse
scientific, clinical or non-clinical presentation or publication or
of child, or sibling or spouse of sibling of the Contributor) by:
participation in Academy leadership or governance, provided
that appropriate disclosure of such relationship is made. Simi- • Direct or indirect compensation;
larly, it should not restrict participation in AAO leadership or • Ownership of stock in the producing company;
governance, so long as appropriate disclosure is made. As an • Stock options and/or warrants in the producing company,
ACCME accredited provider of CME, the Academy seeks to even if they have not been exercised or they are not cur-
ensure balance, independence, objectivity, and scientific rigor in rently exercisable;
all individual or jointly sponsored CME activities. • Financial support or funding to the investigator, including
All contributors to Academy educational and leadership research support from government agencies (e.g., NIH),
activities must disclose all financial relationships (defined below) device manufacturers, and/or pharmaceutical companies;
to the Academy annually. The ACCME requires the Academy to or
disclose the following to participants prior to the activity: • Involvement with any for-profit corporation that is likely
to become involved in activities directly impacting the
• All financial relationships with Commercial Companies
Academy where the Contributor or the Contributor’s fam-
that contributors and their immediate family have had
ily is a director or recipient
within the previous 12 months. A commercial company is
any entity producing, marketing, re-selling or distributing
health care goods or services consumed by, or used on, Description of Financial Interests
patients.
• Meeting presenters, authors, contributors or reviewers Category Code Description
who report they have no known financial relationships to
Consultant / Advisor C Consultant fee, paid advisory
disclose.
boards or fees for attending a
The Academy will request disclosure information from meet- meeting
ing presenters, authors, contributors or reviewers, committee
Employee E Employed by a commercial
members, Board of Trustees, and others involved in Academy
company
leadership activities (“Contributors”) annually. Disclosure infor-
mation will be kept on file and used during the calendar year in Lecture Fees L Lecture and speakers bureau
which it was collected for all Academy activities. Updates to the fees (honoraria), travel fees or
disclosure information file should be made whenever there is a reimbursements when speaking
change. At the time of submission of a Journal article or materi- at the invitation of a commer-
als for an educational activity or nomination to a leadership cial company
position, each Contributor should specifically review his/her
Equity Owner O Equity ownership/stock options
statement on file and notify the Academy of any changes to his/
(publicly or privately traded
her financial disclosures. These requirements apply to relation-
firms, excluding mutual funds).
ships that are in place at the time of or were in place 12 months
preceding the presentation, publication submission, or nomina- Patents / Royalty P Patents and/or royalties that
tion to a leadership position. Any financial relationship that may might be viewed as creating a
constitute a conflict of interest will be resolved prior to the deliv- potential conflict of interest
ery of the activity.
Grant Support S Grant support from all sources
48  2015 Subspecialty Day  |  Neuro-Ophthalmology

Faculty Financial Disclosures

Anne S Abel MD Joseph L Demer MD PhD Andrew G Lee MD

None US Public Health Service, National Eye CredentialProtection: O
Institute: S
Marie D Acierno MD Michael S Lee MD
None Kathleen B Digre MD Eli Lilly & Company: S
None Neuro-ophthalmix: E,P
Anthony C Arnold MD
None Marc J Dinkin MD Leah Levi MD
Alphabiocom: C None
Rudrani Banik MD
National Eye Institute: S Mays A El-Dairi MD Grant T Liu MD
Prana Pharmaceuticals: C None
Jeffrey Bennett MD PhD
AbbVie: C Rod Foroozan MD Collin M McClelland MD
Alnaylam: C Lundbeck: C None
Apsara Therapeutics: C,O
Aquaporumab: P Courtney E Francis MD Neil R Miller MD
Chugai Pharmaceuticals: C None None
EMD Serono: C
Genzyme: C Todd A Goodglick MD Heather Moss MD PhD
Mallinckrodt: S,C None Clearview Healthcare Partners: C
MedImmune: C Eli Lily & Company: S
Novartis Pharmaceuticals Lynn K Gordon MD PhD H Lundbeck A/S: C
Corporation: S,C None Illinois Society for Prevention of
Teva Neuroscience: C Blindness: S
Gena Heidary MD National Eye Institute: S
M Tariq Bhatti MD None Research to Prevent Blindness: S
Novartis Pharmaceuticals Corp.: C,L
Guy V Jirawuthiworavong MD Nancy J Newman MD
Valerie Biousse MD None Gensight: C
GenSight: C Santhera: C
Randy H Kardon MD PhD Trius/Cubist: C
Gabrielle R Bonhomme MD Department of Defense TATRC: S
None Medface: O Jeffrey G Odel MD
National Eye Institute: S Bayer Healthcare Pharmaceuticals: C
Michael C Brodsky MD Novartis Pharmaceuticals Corp.: C Regeneron Pharmaceuticals: C
None Veterans Administration: S
Paul H Phillips MD
John J Chen MD Bradley J Katz MD None
None Axon Optics, LLC: O
Pfizer, Inc.: O Stacy L Pineles MD
Sophia Mihe Chung MD None
Eli Lilly & Company: S Lanning B Kline MD
None John Pula MD
Fiona E Costello MD Questor: C
None Gregory S Kosmorsky DO
None Jacinthe Rouleau MD
Sarita B Dave MD Allergan: C
New York State Department of Jacqueline A Leavitt MD
Health: S None Janet C Rucker MD
None

Disclosures current as of 10/9/2015

Check the online program/mobile meeting guide for the most current financial disclosures
2015 Subspecialty Day  |  Neuro-Ophthalmology Faculty Financial Disclosures 49

Alfredo A Sadun MD PhD Subspecialty Day Jonathan B Rubenstein MD

Edison Pharmaceutical: S Advisory Committee Alcon Laboratories, Inc.: C
Stealth Peptides: S Bausch + Lomb: C,L
William F Mieler MD
Peter J Savino MD Genentech: C R Michael Siatkowski MD
None National Eye Institute: S
Donald L Budenz MD MPH
Harold E Shaw Jr MD Alcon Laboratories, Inc.: C Nicholas J Volpe MD
Abbott Laboratories: O Ivantis: C None
AbbVie: O
Bristol Myers Squibb: O Daniel S Durrie MD
Johnson & Johnson Consumer & Abbott Medical Optics: S AAO Staff
Personal Products Worldwide: O AcuFocus, Inc.: C,L,O,S
Novartis Pharmaceuticals Corp.: O Alcon Laboratories, Inc.: L,O,S Christa Fernandez
Pfizer, Inc.: O Allergan: S None
Alphaeon: C,O
S Tonya Stefko MD Avedro: L,O,S Ann L’Estrange
None Strathspey Crown LLC: C,L,O None
Wavetec: C,O,P
Mitchell B Strominger MD Melanie Rafaty
None Francis S Mah MD None
Abbott Medical Optics Inc.: L
Prem S Subramanian MD PhD Alcon Laboratories, Inc.: C,S Debra Rosencrance
NASA: C Allergan: C,L None
National Eye Institute: S Bausch + Lomb: C,L
Novartis Pharmaceuticals Corp.: S CoDa: C Beth Wilson
US Department of Defense: S ForeSight: C None
Imprimis: C
Gregory P Van Stavern MD Ocular Therapeutix: C,S
None Omeros: C
PolyActiva: C
Nicholas J Volpe MD Shire: C
None TearLab: C

Kimberly M Winges MD
None

Disclosures current as of 10/9/2015

Check the online program/mobile meeting guide for the most current financial disclosures
50  2015 Subspecialty Day  |  Neuro-Ophthalmology

Presenter Index

Acierno, Marie D  2, 28
Bennett*, Jeffrey  6, 31
Bhatti*, M Tariq  23, 43
Bonhomme, Gabrielle R  14, 36
Chen, John J  6, 31
Costello, Fiona E  26, 44
Demer*, Joseph L  17
Dinkin*, Marc J  22, 39
Foroozan*, Rod  11, 34
Francis, Courtney E  15, 38
Goodglick, Todd A  26, 45
Gordon, Lynn K  8, 12
Heidary, Gena  7, 32
Jirawuthiworavong, Guy V  2, 29
Katz*, Bradley J  14, 35
Moss*, Heather  24, 44
Phillips, Paul H  15, 37
Pineles, Stacy L  22, 41
Pula*, John  10, 33
Rouleau*, Jacinthe  3, 30
Rucker, Janet C  16, 38
Sadun*, Alfredo A  4
Shaw*, Harold E  25
Stefko, S Tonya  10, 33
Van Stavern, Gregory P  23, 42
Winges, Kimberly M  21, 39

* Indicates that the presenter has financial interest.

No asterisk indicates that the presenter has no financial interest.