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NeuroOphthalmology 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 Michael S Lee MD Program Director Prem S Subramanian MD PhD Program Director Anne S Abel MD Rudrani Banik MD Sophia Mihe Chung MD Sarita B Dave MD Mays A El-Dairi MD Andrew G Lee MD Collin M McClelland MD Mitchell B Strominger MD Former Program Directors 2013 Andrew G Lee MD Michael S Lee MD 2011 2009 2007 Andrew G Lee MD Karl C Golnik MD Leah Levi MBBS Andrew G Lee MD Karl C Golnik MD Subspecialty Day Advisory Committee William F Mieler MD Associate Secretary Donald L Budenz MD MPH Daniel S Durrie MD Francis S Mah MD R Michael Siatkowski MD Nicolas J Volpe MD Jonathan B Rubenstein MD Secretary for Annual Meeting Staff Melanie R Rafaty CMP, Director, Scientific Meetings Ann L’Estrange, Scientific Meetings Specialist Christa Fernandez, Presenter Coordinator Debra Rosencrance CMP CAE, Vice President, Meetings & Exhibits Patricia Heinicke Jr, Copyeditor Mark Ong, Designer Gina Comaduran, Cover Design ©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 Eli Lilly & Company: S Neuro-ophthalmix: E,P NASA: C National Eye Institute: S Novartis Pharmaceuticals Corp.: S US Department of Defense: S Program Director Program Director Program Planning Group Anne S Abel MD Rudrani Banik MD Sophia Mihe Chung MD None National Eye Institute: S Eli Lilly & Company: S Subspecialty Day Planning Group 2015 Subspecialty Day | Neuro-Ophthalmology No photo available No photo available Sarita B Dave MD Andrew G Lee MD Mitchell B Strominger MD New York State Department of Health: S CredentialProtection: O None Mays A El-Dairi MD Prana Pharmaceuticals: C Collin M McClelland MD None iii 2015 Subspecialty Day | Neuro-Ophthalmology 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 v 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 Continuing Medical Education (CME) program is to present ophthalmologists with the highest quality lifelong learning opportunities that promote improvement and change in physician practices, performance, or competence, thus enabling such physicians to maintain or improve the competence and professional performance needed to provide the best possible eye care for their patients. Teaching instruction courses or delivering a scientific paper or poster is not an AMA PRA Category 1 Credit™ activity and should not be included when calculating your total AMA PRA. Category 1 Credits™: Presenters may claim AMA PRA Category 1 Credits™ through the American Medical Association. Please contact the AMA to obtain an application form at www. ama-assn.org. 2015 Neuro-Ophthalmology Subspecialty Day Meeting Learning Objectives Upon completion of this activity, participants should be able to: • Recognize urgent signs and symptoms in the evaluation of adults with diplopia • Direct the initial workup of a patient with visual loss from optic neuropathy • Distinguish the key findings in the management of eye pain and associated headache • Determine when and how to order neuroimaging studies for ophthalmic conditions 2015 Neuro-Ophthalmology Subspecialty Day Meeting Target Audience The intended audience for this program is comprehensive ophthalmologists. 2015 Neuro-Ophthalmology Subspecialty Day Meeting CME Credit The American Academy of Ophthalmology is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians. The American Academy of Ophthalmology designates this live activity for a maximum of 7 AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate with the extent of their participation in the activity. ABO Self-Assessment Credit This activity meets the Self-Assessment CME requirements defined by the American Board of Ophthalmology (ABO). Please be advised that the ABO is not an accrediting body for purposes of any CME program. The ABO does not sponsor this or any outside activity, and the ABO does not endorse any particular CME activity. Complete information regarding the ABO SelfAssessment CME Maintenance of Certification requirements is available at http://abop.org/maintain-certification/part-2-lifelong-learning-self-assessment/cme/. NOTE: Credit designated as “self-assessment” is AMA PRA Category 1 Credit™ and is also preapproved by the ABO for the Maintenance of Certification (MOC) Part II CME requirements. Scientific Integrity and Disclosure of Financial Interest The American Academy of Ophthalmology is committed to ensuring that all CME information is based on the application of research findings and the implementation of evidence-based medicine. It seeks to promote balance, objectivity, and absence of commercial bias in its content. All persons in a position to control the content of this activity must disclose any and all financial interests. The Academy has mechanisms in place to resolve all conflicts of interest prior to an educational activity being delivered to the learners. The Academy requires all presenters to disclose on their first slide whether they have any financial interests from the past 12 months. Presenters are required to verbally disclose any financial interests that specifically pertain to their presentation. Attendance Verification for CME Reporting Before processing your requests for CME credit, the Academy must verify your attendance at Subspecialty Day and/or at AAO 2015. In order to be verified for CME or auditing purposes, you must either: • Register in advance, receive materials in the mail, and turn in the Final Program and/or Subspecialty Day Syllabus exchange voucher(s) onsite; • Register in advance and pick up your badge onsite if materials did not arrive before you traveled to the meeting; or • Register onsite. CME Credit Reporting Level 2; Academy Resource Center, Hall B, Booth 2632 Attendees whose attendance has been verified (see above) at AAO 2015 can claim their CME credit online during the meeting. Registrants will receive an email during the meeting with a link and instructions on how to claim credit. Onsite, you may report credits earned during Subspecialty Day and/or AAO 2015 at the CME Credit Reporting booth. Academy Members: The CME credit reporting receipt is not a CME transcript. CME transcripts that include AAO 2015 credits entered onsite will be available to Academy members on the Academy’s website beginning Dec. 10, 2015. NOTE: CME credits must be reported by Jan. 13, 2016. After AAO 2015, credits can be claimed at www.aao.org. The 2015 Subspecialty Day | Neuro-Ophthalmology 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 Academysponsored 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. CME Credit vii viii 2015 Subspecialty Day | Neuro-Ophthalmology Faculty Anne S Abel MD Rudrani Banik MD Valerie Biousse MD Wayzata, MN Neuro-Ophthalmologist Hennepin County Medical Center, Minneapolis, MN New York, NY Associate Adjunct Surgeon The New York Eye & Ear Infirmary Associate Professor of Ophthalmology New York Medical College Atlanta, GA Professor of Ophthalmology and Neurology Emory University School of Medicine No photo available Marie D Acierno MD Baton Rouge, LA Professor of Ophthalmology Residency Director of Ophthalmology LSU Health Sciences Center/Ochsner, New Orleans Anthony C Arnold MD Los Angeles, CA Professor and Chief Neuro-Ophthalmology Division Jules Stein Eye Institute Jeffrey Bennett MD PhD Aurora, CO Professor of Neurology and Ophthalmology University of Colorado School of Medicine M Tariq Bhatti MD Durham, NC Professor of Ophthalmology and Neurology Duke University Eye Center and Duke University Medical Center Gabrielle R Bonhomme MD Pittsburgh, PA Assistant Professor of Ophthalmology University of Pittsburgh M.D. University of Pittsburgh Medical Center Michael C Brodsky MD Rochester, MN Professor of Ophthalmology and Neurology Mayo Clinic Faculty Listing 2015 Subspecialty Day | Neuro-Ophthalmology ix No photo available John J Chen MD Sarita B Dave MD Marc J Dinkin MD Rochester, MN Assistant Professor Mayo Clinic Jersey City, NJ Neuro-Ophthalmologist, ECRIP Investigator New York Eye and Ear Infirmary of Mount Sinai New York, NY Assistant Professor of Ophthalmology and Director of NeuroOphthalmology 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 & Psychiatry, and Neurosurgery Saint Louis University School of Medicine Joseph L Demer MD PhD Los Angeles, CA Leonard Apt Professor of Ophthalmology Professor of Neurology David Geffen Medical School University of California, Los Angeles Director of Ocular Motility Laboratory Stein Eye Institute University of California, Los Angeles Mays A El-Dairi MD Durham, NC Assistant Professor Duke Eye Center Fiona E Costello MD Calgary, AB, Canada Associate Professor Department of Clinical Neurosciences and Surgery University of Calgary, Hotchkiss Brain Institute Clinician-Scientist Hotchkiss Brain Institute Rod Foroozan MD Kathleen B Digre MD Salt Lake City, UT Professor, Neurology and Ophthalmology Moran Eye Center University of Utah Houston, TX Associate Professor of Ophthalmology Baylor College of Medicine x Faculty Listing 2015 Subspecialty Day | Neuro-Ophthalmology Courtney E Francis MD Gena Heidary MD Bradley J Katz MD Seattle, WA Assistant Professor Department of Ophthalmology University of Washington Cambridge, MA Director, Pediatric Neuro Ophthalmology Service Boston Children’s Hospital Assistant Professor in Ophthalmology Harvard Medical School Salt Lake City, UT Associate Professor of Ophthalmology and Neurology University of Utah Todd A Goodglick MD Chevy Chase, MD Department of Ophthalmology Georgetown University/Washington Hospital Center Washington Eye Physicians Lanning B Kline MD Guy V Jirawuthiworavong MD Torrance, CA Regional Neuro-Ophthalmologist Uveitis Consultant & Medical Retinologist Southern California Kaiser Permanente Medical Group Birmingham, AL Professor of Ophthalmology University of Alabama at Birmingham Gregory S Kosmorsky DO Highland Heights, OH Head, Section of Neuro-Ophthalmology Cleveland Clinic Lynn K Gordon MD PhD Los Angeles, CA Professor of Ophthalmology Jules Stein Eye Institute, David Geffen School of Medicine University of California, Los Angeles Senior Associate Dean, Diversity Affairs David Geffen School of Medicine University of California, Los Angeles Randy H Kardon MD PhD Iowa City, IA Professor of Ophthalmology and Director of Neuro-Ophthalmology University of Iowa 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 Consultant Mayo Clinic Associate Professor of Ophthalmology Mayo Medical School La Jolla, CA Director of Neuro-Ophthalmology Scripps Clinic Division of Ophthalmology Baltimore, MD Frank B Walsh Professor of NeuroOphthalmology Wilmer Eye Institute Johns Hopkins University School of Medicine Professor of Ophthalmology, Neurology and Neurosurgery Johns Hopkins University School of Medicine Andrew G Lee MD Grant T Liu MD Houston, TX Professor of Ophthalmology, Neurology, and Neurosurgery Weill Cornell Medical College Chairman of Ophthalmology Houston Methodist Hospital, Blanton Eye Institute Philadelphia, PA Neuro-Ophthalmology Service Division of Ophthalmology Children’s Hospital of Philadelphia Division of Neuro-Ophthalmology, Department of Neurology Hospital of the University of Pennsylvania Michael S Lee MD Collin M McClelland MD Minneapolis, MN Professor, Departments of Ophthalmology, Neurology and Neurosurgery University of Minnesota Saint Louis, MO Assistant Professor of NeuroOphthalmology Department of Ophthalmology Washington University in St. Louis Heather Moss MD PhD Chicago, IL Assistant Professor of Ophthalmology and Visual Sciences Clinical Assistant Professor of Neurology and Rehabilitation University of Illinois at Chicago Nancy J Newman MD Atlanta, GA LeoDelle Jolley Professor of Ophthalmology Professor of Ophthalmology and Neurology Emory University School of Medicine xii Faculty Listing No photo available 2015 Subspecialty Day | Neuro-Ophthalmology No photo available Jeffrey G Odel MD John Pula MD Alfredo A Sadun MD PhD New York, NY Professor of Ophthalmology Columbia University Medical Center Chicago, IL Clinician, Northshore University Healthsystem Associate Professor University of Chicago College of Medicine Pasadena, CA F Thornton Chair Department of Ophthalmology Doheny Eye Institute University of California, Los Angeles Paul H Phillips MD Little Rock, AR Professor of Ophthalmology University of Arkansas for Medical Sciences Chief-of-Staff Department of Ophthalmology Arkansas Children’s Hospital Jacinthe Rouleau MD Montreal, QC, Canada Clinical Assistant Professor and Chief, Neuro-Ophthalmology Section Université de Montréal Peter J Savino MD La Jolla, CA Professor of Neuro-Ophthalmology Shiley Eye Institute University of California, San Diego No photo available Stacy L Pineles MD Janet C Rucker MD Los Angeles, CA Assistant Professor of Ophthalmology University of California, Los Angeles New York, NY Associate Professor of Neurology New York University School of Medicine Harold E Shaw Jr MD Greenville, SC Practicing Ophthalmologist Jervey Eye Group, P.A. Clinical Assistant Professor 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 Assistant Professor of Ophthalmology and Neurological Surgery University of Pittsburgh Medical Center Baltimore, MD Professor of Ophthalmology, Neurology, and Neurosurgery University of Colorado School of Medicine Associate Professor of Surgery Uniformed Services University of the Health Sciences Chicago, IL George and Edwina Tarry Professor of Ophthalmology and Chairman Feinberg School of Medicine Northwestern University No photo available Mitchell B Strominger MD Boston, MA Professor of Ophthalmology and Pediatrics Tufts University School of Medicine Kimberly M Winges MD Gregory P Van Stavern MD St Louis, MO Associate Professor Department of Ophthalmology and Visual Sciences Washington University in St. Louis Portland, OR Neuro-Ophthalmologist Veterans Affairs Health System Assistant Professor of Ophthalmology and Neurology Casey Eye Institute Oregon Health and Sciences University 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 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* 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* 9:55 AM REFRESHMENT BREAK and AAO 2015 EXHIBITS Michael S Lee MD* 4 8 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 Ridiculously Simple Lynn K Gordon MD PhD* 11:20 AM “The light!! It hurts my eyes!!” Bradley J Katz MD* 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. 12 14, 35 2015 Subspecialty Day | Neuro-Ophthalmology xv Program Schedule 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* 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* 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. 17 25 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.” Marie D Acierno MD C ase “I am slowly losing vision in one of my eyes.” Guy V Jirawuthiworavong MD C ase History and Exam Twenty-year-old male reports left eye dull pain with eye movements and a constant headache that began one week ago. Several days later he noticed blurred vision in his left eye. The vision gradually worsened over 1 to 2 days. He denies any involvement in the other eye. He has had no recent viral-like illness or associated symptoms. His past medical history is noncontributory. On examination, his visual acuity is 20/20 O.D. and 20/80 O.S. with a left relative afferent pupillary defect, dyschromatopsia, and a left central scotoma. Slitlamp biomicroscopy and IOPs are normal. The funduscopic examination reveals a normal appearing right optic disc and left optic disc edema. There are no macular lesions, and the vitreous is clear in either eye. Clinical Course and Outcome The patient had an MRI brain/orbit imaging study with gadolinium with fat suppression revealing enhancement of the left optic nerve. His pain with eye movements began to subside shortly after clinical presentation. The patient received a 3-day course of IV steroids at an outpatient infusion center. His vision in the left eye was 20/30 at 4 weeks after the onset, with subjective improvement in his color vision. At 6 months, his visual acuity was 20/20 in each eye with no apparent relative afferent pupillary defect, subtle left optic disc atrophy, and retinal nerve fiber layer thinning by OCT in the left eye compared to the right eye. History and Exam Fifty-three-year-old automotive saleswoman noted unilateral, progressive loss of vision in the right eye over the last year. Her visual problems began in her early 20s, when she experienced flashes of lights and “blank spots” in her vision. Multiple eye examinations were unrevealing. A few years ago, she noted more flashes, numerous dots, and a kaleidoscope of colors in her vision with more significant progression over the past 6 months. She was discovered to have a visual field defect by a retina specialist 3 years ago, but records were not available. She was uncertain about a prior diagnosis of retinitis pigmentosa. She complains of difficulty seeing at night and photophobia. Past medical history is significant for fibromyalgia, eczema, anxiety, and depression. Family history is significant for glaucoma in her late father, who “died of arthritis,” and ulcerative colitis in her son. She denies family members needing a white cane or a seeing eye dog. Review of systems reveals an occasional headache and Raynaud phenomenon that she describes as painfully cold fingers. She denies any numbness or weakness. Her current medications are tramadol, alprazolam, and citalopram. On examination, patient is a mild hyperope with BCVA of 20/25 O.D. and 20/20 O.S. Color vision is intact. She has a 2+ afferent pupillary defect on the right. Her confrontational fields reveal a temporal defect in the right eye and a normal field in 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 fluorescein angiogram were completed. Extensive blood testing for infectious and inflammatory conditions did not reveal any contributory 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 epithelial abnormalities with window defects. Watchful observation 2015 Subspecialty Day | Neuro-Ophthalmology was recommended. Patient’s visual field remained stable, with sequential 30-2 and 10-2 visual field testing. Patient was assured of the findings and that her condition was consistent with acute zonal occult outer retinopathy (AZOOR). She used tinted glasses to help decrease her photophobia. “My doctor says I might have glaucoma.” Jacinthe Rouleau MD C ase History and Exam A 75-year-old male is referred by his family doctor for suspicion of glaucoma because his confrontation visual field is abnormal inferiorly in the left eye. The patient complains about a vague sensation of blurry vision in the left eye present for 4 months. He can’t remember exact onset but it’s now stable. He has no headache or other neurological symptoms. Three months ago an optometrist told him that his visual field was abnormal O.S. and recommended that he see an ophthalmologist. However, the patient failed to do so, discussing his eye problem with his general practitioner instead. His past medical history is significant for hypertension, hyperlipidemia, and cardiac stenting 4 years ago. His medications include lisinopril, metoprolol, atorvastatin, aspirin, and clopidogrel. He is a nonsmoker. His family history is positive for a sister with glaucoma. On examination, his BCVA is 20/25 O.D. and 20/40 O.S. IOP is 21 in both eyes, with pachymetry of 537 and 542 microns O.D. and O.S., respectively. A relative afferent pupillary defect (RAPD) is present O.S. Ocular motility is full. Anterior segment is normal except for moderate nuclear sclerosis in both eyes. Gonioscopy reveals open angles in both eyes. Color vision is decreased O.S. with HRR plates (O.D. 10/10 and 5.5/10 O.S). Visual field testing is normal O.D., but there is an inferior altitudinal visual field defect O.S. Examination of the optic nerves showed asymmetric cup-to-disc ratios. The maculae and peripheral retina are normal. Clinical Course and Outcome The cup-to-disc ratio of the right optic nerve is 0.2, while the left is 0.5 with suspicion of pallor superiorly. OCT shows asymmetric cupping, and the left eye has thinning of the nerve fiber layer superiorly and temporally. MRI of brain and orbits with gadolinium, obtained by his family doctor, was normal 2 weeks previously. Complete blood count, erythrocytes sedimentation rate, and C-reactive protein were also normal. Various causes of optic neuropathy can be mistaken for glaucoma: compressive \ infiltrative, ischemic (both arteritic and nonarteritic), congenital, hereditary, post-traumatic, demyelinating, or toxic. Some red flags should raise suspicion for nonglaucomatous cupping: pallor of the remaining rim, vertically aligned field defects or other atypical visual fields defects for glaucoma (central or cecocentral), marked RAPD, asymmetrical loss of color vision, asymmetric cupping, especially without history of asym- Section I: Vision Loss 3 metric IOP, visual acuity less than 20/40, and patient younger than 50 years of age. Because compressive or infiltrative lesions of the optic nerve can mimic visual field loss from glaucoma, neuroimaging, preferably MRI of the brain and orbits with gadolinium contrast and fat suppression, is warranted in any suspicious or atypical presentation. In our case, some clues raise the suspicion for a nonglaucomatous optic neuropathy. The optic disc demonstrates prominent pallor with less severe excavation and notching than in glaucoma. Moreover, the severity of the visual field loss inferiorly does not match the degree of the notching superiorly. The presence of the RAPD and the asymmetry in visual acuity also raise suspicion, especially with the absence of asymmetric IOP or pachymetry. In addition, the decreased color vision O.S. is another red flag for a neuro-ophthalmologic pathology. Alternatively, the presence of structural crowding of the contralateral disc (disc at risk of 0.2) and systemic hypertension and hyperlipidemia favor the diagnosis of an old nonarteritic anterior ischemic optic neuropathy (NAION). Other potential risk factors are diabetes, sleep apnea, generalized hypoperfusion, severe anemia, nocturnal hypotension, and medications (amiodarone and erectile dysfunction agents). Previous ischemic optic neuropathy may present with nerve fiber bundle field loss and optic atrophy if seen after the disc swelling resolves. Increased cupping can be seen as sequelae of both arteritic and nonarteritic forms of ischemic optic neuropathy, although it is more often seen in the arteritic form. In our case, the diagnosis of arteritic anterior ischemic optic neuropathy is unlikely given the normal blood tests and the absence of systemic symptoms of giant cell arteritis (headache, jaw claudication, weight loss, anorexia, or fever). NAION constitutes 95% of all anterior ischemic optic neuropathies and is the most common cause of acute optic neuropathy in people over the age of 50. Because of its prevalence, previously undiagnosed NAION with optic atrophy can be seen on routine ophthalmologic exam. When prior NAION is suspected, efforts should be made to document the acute initial disc edema by reviewing prior medical records. In our case, acute optic disc swelling is documented on the fundus pictures taken 3 months ago by his optometrist and confirms our diagnosis. Other causes of nonglaucomatous cupping include methanol poisoning or genetic optic neuropathies like Leber hereditary 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 likely to present as sequential bilateral optic neuropathy, while the methanol poisoning and DOA have relatively symmetric involvement of the optic nerves. Additionally, in the presence of altitudinal field defect, a complete examination of the posterior pole and peripheral retina is always important to rule out retinal pathology such as retinal detachment or branch retinal vein or artery occlusion. 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 not so much an exercise in compulsive detail as it is in asking the right question, one that enables the clinician to test the hypothesis. Hence, the best history is obtained by knowing the general principles of neuro-ophthalmology, applying critical aspects of anatomy and physiology, and having a clear understanding of the differential diagnosis. This differential diagnosis begins broadly and proceeds to the narrow based on answers to the questions posed. In particular, in cases of possible optic neuropathy, the following questions are most important: 1. Does the patient see things as dark (brown or grey) as opposed to distorted or blurred? Loss of retinal ganglion cells (RGCs) or their axons in the optic nerve decreases the sense of brightness. In contradistinction, maculopathies often cause metamorphopsia, problems with the ocular media, and refractive problems, blurred vision. 2. Is there a subjective loss of color vision? Dyschromatopsia is frequently the seminal symptom in optic neuropathies. If the answers to questions 1 and 2 are positive, assume that there is an optic neuropathy. Most optic neuropathies are ischemic, inflammatory, compressive, or metabolic. 3. What is the tempo or cadence of visual loss? Vascular injuries come on abruptly. Inflammatory conditions are more likely to be subacute. Metabolic and compressive injuries are likely to progress slowly. 4. Is the condition unilateral or bilateral? Unless there is a chiasmal or postchiasmal lesion, bilateral conditions speak to metabolic and, less likely, inflammatory conditions. If the answers to 3 and 4 suggest slow progressive bilateral loss of vision, then the main differential diagnosis is between a parasellar mass and metabolic optic neuropathy. But nonorganic vision loss should always be considered, especially in the absence of signs. Other useful questions include pain, pain with eye movements, and other, especially neurological, associated symptoms. Let us assume, at this stage, that we have a 68-year-old woman with painless loss of vision characterized first by loss of color, who sees a dark splotch in the center of her vision bilaterally. The visual loss came on over a period of several months. But the referring physician did not note abnormalities on fundus examination. What should we concentrate on in the neuro-ophthalmological examination? Key elements in this examination are the following: 1.Pupils Are the reactions sluggish? Is there an afferent pupillary defect (APD)? In this case, no. 2. Optic disc appearance on fundus examination Is there subtle evidence of disc edema, papillitis, telangiectasis of peripapillary vessels, or arteriolar attenuation? Is there nerve fiber layer thinning or thickening, and does the macula have any abnormalities? None of these findings were evident. 3. Visual field pattern Are the central scotomas symmetrical? Is there respect for the vertical or horizontal raphes? In this case, small central scotomas crossing both the horizontal and vertical raphes were seen. In this patient, the pupils were normal; there was no APD. And there was no optic disc edema or frank optic atrophy, though there was perhaps slight temporal pallor. The macular reflex was normal. These findings are consistent with the diagnoses of parasellar mass, metabolic and non-organic, considered above. Non-organic vision loss should not be a diagnosis of exclusion. There are several tests that can help us find deliberate malingering and even evidence of conversion reaction hysteria. An intracranial mass, especially in the area of the chiasm, can be easily found by neuroimaging. However, the visual acuities were worse than 20/400 O.U., unlikely to be seen in a chiasmal syndrome. Furthermore, the visual fields showed scotomas in both the nasal and temporal side. Further questioning revealed that the patient was not currently on any known toxic agent and had a good diet. How then to proceed with specialized testing? 1. HVF 30-2 vs. 10-2 The 24-2 program is good for glaucoma screening and monitoring. But the 30-2 gives a better indication of how the defect may emerge from the blind spot, and the 10-2 is good for detailing the shape of the central scotoma. 2. Red Amsler grid testing This is especially useful when the central scotoma is small and shallow. Testing for both red and contrast in the central area can be very helpful in toxic / metabolic optic neuropathies. 3. OCT for macula, retinal nerve fiber layer (RNFL) and ganglion cell layer (GCL) The RNFL showed slight thinning temporally O.U. But OCT is not very sensitive for the RNFL in this quadrant. More obvious was thickening of the RNFL in the inferior temporal areas O.U. The macula was clear of any cysts, edema, or structural alterations. However the GCL was bilaterally and symmetrically thinned. 4. MRI, etc. In this case, MRI or other neuroimaging would not be that helpful. Getting unnecessary imaging opens the Pandora’s box for both false positives and, more importantly, hyperdiagnosis (real lesions that have no bearing on the patient’s symptoms). Unwarranted anxiety, additional testing, biopsies, and even neurosurgical interventions have been known to follow MRIs that should not have been ordered insofar as an intracranial lesion was already outside the confines of the differential diagnosis. Section I: Vision Loss 2015 Subspecialty Day | Neuro-Ophthalmology In the aggregate, bilateral GCL thinning, especially in the setting of RNFL thickening inferior temporally, is highly specific for mitochondrial optic neuropathy. While the papillomacular bundle is poorly visualized by OCT RNFL, GCL thickness in the macula, especially in comparison to RNFL thickness, provides very helpful information in the detection, characterization, and monitoring of both genetic and acquired forms of mitochondrial optic neuropathies. This was demonstrated in glaucoma and, more recently, in both genetic and acquired forms of mitochondrial optic neuropathy. In the case described above, the patient had been on ethambutol for about 6 months when she first noted vision loss. Her dosing was too high, especially in light of her compromised kidney function (creatinine of 1.4). Her ophthalmologist discontinued the ethambutol, but the vision loss progressed such that by 8 months, her vision fell to counting fingers O.U. It was then that she presented to us not “currently” on any toxic medication. However, persistent or even progressively worsening vision after discontinuation of therapy is not uncommon in ethambutol toxicity, which is an acquired form of mitochondrial optic neuropathy. The patient began to recover at 9 months and returned to 20/25 after 1-2 years. This case serves to remind us of the value of history taking 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. 5 Selected Readings 1. Sadun AA. Mitochondrial optic neuropathies. J Neurol Neurosurg Psychiatry. 2002; 72(4):423-425. 2. Sadun A. Acquired mitochondrial impairment as a cause of optic nerve disease. Trans Am Ophthalmol Soc. 1998; 96:881-923. 3. Zoumalan CI, Sadun AA. Optical coherence tomography can monitor reversible nerve-fibre layer changes in a patient with ethambutol-induced optic neuropathy. Br J Ophthalmol. 2007; 91(6):839840. 4. Barboni P, Savini G, Valentino ML, Montagna P, Cortelli P, De Negri AM, Sadun F, Bianchi S, Longanesi L, Zanini M, de Vivo A, Carelli V. Retinal nerve fiber layer evaluation by optical coherence tomography in Leber’s hereditary optic neuropathy. Ophthalmology 2005; 112(1):120-126. 5. Barboni P, Savini G, Cascavilla ML, Caporali L, Milesi J, Borrelli E, La Morgia C, Valentino ML, Triolo G, Lembo A, Carta A, De Negri A, Sadun F, Rizzo G, Parisi V, Pierro L, Bianchi Marzoli S, Zeviani M, Sadun AA, Bandello F, Carelli V. Early macular retinal ganglion cell loss in dominant optic atrophy: genotype-phenotype correlation. Am J Ophthalmol. 2014; 158(3):628-636. 6 Section I: Vision Loss “I lose my vision and then it comes back.” Jeffrey Bennett MD PhD 2015 Subspecialty Day | Neuro-Ophthalmology “I’m losing vision in both eyes.” John J Chen MD C ase C ase History and Exam History and Exam A 57-year-old woman presented with a 1-month history of transient, painless vision loss in the right eye. The episodes lasted an average of 5-10 minutes, but some lasted longer. The events typically began with flashing lights and progressed to light perception vision. The episodes occurred sporadically and in rare instances happened more than once in a single day. There were no concurrent ophthalmologic or neurologic symptoms. Between events, the vision in her right eye remained slightly blurred. The patient’s past medical history was notable for hypertension, and her current medications included enalapril and estrogen. Family and social history were unremarkable. Review of systems revealed no fevers, chills, night sweats, temporal artery tenderness, polymyalgia, or jaw claudication. On examination, visual acuities were 20/30 right eye and 20/20 left eye, with subjective color desaturation in the right eye. Visual fields were full, and pupils were briskly reactive to light without an afferent pupillary defect. Motility was normal and dilated exam showed no evidence of optic disc or retinal abnormalities. Clinical Course and Outcome Following the fundus examination, the patient experienced an episode of vision loss in the right eye. Visual acuity dropped to light perception in the right eye, and the right pupil dilated slightly and became sluggishly reactive to light with an associated right afferent defect. Fundus exam showed constriction of retinal arterioles with sluggish flow in retinal bed and segmental constriction of retinal veins with “box-carring.” Subsequent laboratory studies showed a normal complete blood count, erythrocyte sedimentation rate, C-reactive protein, and comprehensive metabolic profile. Serology was negative for antinuclear antigen and anti-neutrophil cytoplasmic antibody. MRI brain and MR angiography of the neck were normal. Echocardiography showed normal function, and bubble study was negative. The patient was treated with verapamil and had no further events. A 54-year-old female with a 2-year history of normal-tension glaucoma was referred for bilateral progressive visual loss. One year prior to presentation, she developed painless, progressive vision loss in the left eye that kept progressing despite cataract surgery. This prompted bilateral trabeculectomies with singledigit IOP outcomes. However, she continued to develop painless, progressive vision loss in the right eye 6 months later, which led to a referral to neuro-ophthalmology for further evaluation. The patient was no longer able to work as a nurse or drive. Other than the vision loss, she was asymptomatic. Her past medical history is significant for hyperlipidemia and depression. Medications include simvastatin and sertraline. On examination, BCVA was CF O.D. and HM O.S. There was a 2.1 log unit relative afferent pupillary defect O.S. IOPs were 1 O.D. and 6 O.S. (mmHg). Slitlamp examination showed a large elevated bleb superiorly O.U., mild cataract O.D., and pseudophakia O.S. Fundus examination revealed a cup-to-disc ratio of 0.9 O.D. and 0.95 O.S. Clinical Course and Outcome Goldmann visual fields showed dense central scotoma and nasal loss, bilaterally. OCT showed severe thinning of the retinal nerve fiber layer O.U. with mild chorioretinal folds O.D. Detailed fundus examination revealed pallor of the remaining rim O.S. The patient underwent an MRI that showed a large sellar mass with compression of the chiasm and optic nerves. She underwent bifrontal craniotomy 1 week later with gross resection revealing a WHO grade II chordoid meningioma. She noticed instant improvement in the vision O.D. following the surgery. Examination 2 months later showed her vision improved from CF to 20/60 O.D. O.S. remained HM. Visual fields showed a prominent nasal step consistent with underlying glaucoma. 2015 Subspecialty Day | Neuro-Ophthalmology “Can my child see?” Gena Heidary MD PhD C ase History and Exam A 2-month-old baby girl presented to the neuro-ophthalmology clinic for unusual eye movements and poor visual behavior. The parents have noted that she does not look at her mother while nursing. Birth history She was born full term at 38 weeks to a 16-year-old G2P0 mother. The pregnancy was uncomplicated. Maternal medical history No known medical illnesses. Prenatal vitamins were used throughout the pregnancy. Family history Noncontributory. Social history Mother and father are from El Salvador and currently reside in the United States. There is no history of consanguinity. Section I: Vision Loss 7 Exam Vision: Light averse in each eye. No response to 20/2400 card on preferential looking testing and unable to elicit response to the optokinetic nystagmus drum. Cycloplegic refraction was +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 normal, without evidence of a relative afferent pupillary defect. Anterior segment examination was normal in each eye. A dilated fundus examination revealed bilateral abnormalities involving the optic nerves. Foveae were normal. Clinical Course and Outcome In the setting of bilateral optic nerve hypoplasia, neuroimaging and a complete endocrinologic workup were pursued. MRI revealed absence of the septum pellucidum and thinning of the optic nerves more prominently involving the right optic nerve. The pituitary appeared normal radiographically. A full endocrinologic evaluation was normal. The infant began working with a teacher for visual impairment through Early Intervention, with gradual improvement of vision. Patching of the dominant left eye was initiated to facilitate visual development in the right eye. She was followed at regular intervals to monitor visual development. At the most recent follow-up at age 4, visual acuity is 20/300 right eye and 20/200 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 remains a key priority for the Academy. All ophthalmologists should consider their contributions to the following three funds as (a) part of their costs of doing business and (b) their individual responsibility in advocating for patients and their profession: • Surgical Scope Fund (SSF) • OPHTHPAC® Fund • State Eye PAC Your ophthalmologist colleagues serving on Academy committees—the Surgical Scope Fund Committee, the Secretariat for State Affairs, and the OPHTHPAC Committee—are committing many hours on your behalf. The Secretariat for State Affairs is collaborating closely with state ophthalmology society leaders to protect Surgery by Surgeons at the state level. Meanwhile, the OPHTHPAC Committee is hard at work identifying congressional advocates in each state to maintain close relationships with federal legislators in order to advance ophthalmology and patient causes. Both groups’ ultimate goals are to ensure robust funds for both the SSF and the OPHTHPAC Fund so that they are able to (a) protect quality patient eye care, (b) protect ophthalmology practices from payment cuts, (c) reduce burdensome regulations, and (d) advance the profession by promoting funding for vision research and expanded inclusion of ophthalmology in public and private programs. These committed ophthalmologists serving on your behalf have a simple message to convey: “We also need you”! • We need you to contribute to each of these three funds. • We need you to establish relationships with state and federal legislators. • We need you to help us protect quality patient eye care and the profession. Surgical Scope Fund The Surgical Scope Fund (SSF) provides grants to state ophthalmology societies to support their legislative, regulatory, and public education efforts to derail optometric surgery proposals that pose a threat to patient safety, quality of surgical care, and surgical standards. Since its inception, the Surgery by Surgeons campaign—in partnership with state ophthalmology societies and with support from the SSF—has helped 32 state/territorial ophthalmology societies reject optometric surgery proposals. As of July 1, 2015, the Secretariat for State Affairs, in collaboration with the California Academy of Eye Physicians and Surgeons (CAEPS) and the California Medical Society, continues to battle an onerous optometric surgery scope of practice bill (SB 622) in the Golden State. The Secretariat has reached out to all ophthalmology subspecialty society partners to help in this effort, and several have stepped up to the plate. In addition, ophthalmology leaders at California academic institutions have played a critical role by voicing their concerns about the California surgery bill and the impact it would have on quality eye care for patients. A June 24 op-ed in the San Francisco Examiner aptly focused on these leaders’ concerns with its headline “Quality surgical eye care ensured through training.” CAEPS has benefitted from contributions to the SSF, having received significant support from the fund. Other state ophthalmology societies have also benefitted from SSF distributions in 2015 and were able to successfully implement patient safety advocacy campaigns to defeat attempts by optometry to expand its scope of practice to include surgery. The Texas Ophthalmological Association was successful in its patient advocacy and public education efforts to defeat three different optometric-backed surgical scope expansion bills in the Texas state legislature. In addition, the Academy supported the Alaska Society of Eye Physicians and Surgeons in opposing optometric surgery scope legislation that posed a threat to patient surgical care. If enacted, the optometric surgery bill would have authorized optometrists in Alaska to perform surgery with lasers, scalpels, and needles, and to perform other surgical procedures. The legislation would also have allowed optometrists to perform all injections except intravitreal and to prescribe any controlled substances. Thanks to an effective Surgery by Surgeons advocacy campaign, with support from the SSF, this legislation died in committee. The Alaska state legislature adjourned for the year on April 27. The Academy relies not only on the financial contributions to the SSF from individual ophthalmologists and their business practices, but also on the contributions made by ophthalmic state, subspecialty, and specialized interest societies. Several subspecialty societies contributed to the Surgical Scope Fund in 2014, and the Academy counts on their contributions in 2015. OPHTHPAC® Fund OPHTHPAC is a crucial part of the Academy’s strategy to protect and advance ophthalmology’s interests in key areas including physician payments from Medicare as well as protecting ophthalmology from federal scope of practice threats. Established in 1985, OPHTHPAC is one of the oldest, largest, and most successful political action committees in the physician community and is very successful in representing your profession to the U.S. Congress. As one election cycle ends, a new one starts. OPHTHPAC is always under financial pressure to support our incumbent friends as well as to make new friends with candidates. These relationships allow us to have a seat at the table and legislators willing to work on issues important to us and our patients. Among the significant achievements of OPHTHPAC are the following: • Repealed the flawed Sustainable Growth Rate (SGR) formula • Blocked the unbundling of the Medicare global surgery fee period • Removed a provision in fraud and abuse legislation that targeted eyelid surgery • Protected your ability to perform in-office ancillary services Advocating for Patients 2015 Subspecialty Day | Neuro-Ophthalmology Surgical Scope Fund OPHTHPAC® Fund State Eye PAC To derail optometric surgical scope of practice initiatives that threaten patient eye safety and quality of surgical care Ophthalmology’s interests at the federal level Support for candidates for State House and Senate Political grassroots activities, lobbyists and media Campaign contributions, legislative education Campaign contributions, legislative education Contributions: Limited to $5,000 Contribution limits vary based on state regulations. Contributions above $200 are on the public record. Contributions are on the public record depending upon state statutes. Support for candidates for U.S. Congress No funds may be used for candidates or PACs. Contributions: Unlimited Individual, practice, and organization Contributions are 100% confidential. • Working to reduce the burdens from Medicare’s existing quality improvement programs such as the Electronic Health Record Meaningful Use program • Working in collaboration with subspecialty societies to preserve access to compounded and repackaged drugs such as bevacizumab Leaders of the North American Neuro-Ophthalmology Society (NANOS) are part of the American Academy of Ophthalmology’s Ophthalmic Advocacy Leadership Group (OALG), which has met every January for the past eight years in the Washington D.C. area to provide critical input and to discuss and collaborate on the Academy’s advocacy agenda. The topics discussed at the 2015 OALG meeting included collaborative efforts on the IRIS Registry and quality reporting under Medicare. As a 2015 Congressional Advocacy Day (CAD) partner, NANOS ensured a strong presence of neuro-ophthalmology specialists to support ophthalmology’s priorities as nearly 400 Eye M.D.s had scheduled CAD visits to members of Congress in conjunction with the Academy’s 2015 Mid-Year Forum in Washington. NANOS remains a crucial partner with the Academy in its ongoing federal and state advocacy initiatives. State Eye PAC It is also important for all ophthalmologists to support our respective State Eye PACs because state ophthalmology societies cannot count on the Academy’s SSF alone. The presence of a strong State Eye PAC providing financial support for campaign contributions and legislative education to elect ophthalmologyfriendly 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. ACTION REQUESTED: ADVOCATE FOR YOUR PATIENTS!! Academy Surgical Scope Fund contributions are used to support the infrastructure necessary in state legislative / regulatory battles and for public education. PAC contributions are necessary at the state and federal level to help elect officials who will support the interests of our patients. Contributions to each of these three funds are necessary and should be considered the costs of doing business. SSF contributions are completely confidential and may be made with corporate checks or credit cards, unlike PAC contributions, which must be made by individuals and are subject to reporting requirements. Please respond to your Academy colleagues who are volunteering their time on your behalf to serve on the OPHTHPAC* and Surgical Scope Fund** Committees, as well as your state ophthalmology society leaders, when they call on you and your subspecialty society to contribute. Advocate for your patients now! *OPHTHPAC Committee Donald J Cinotti MD (NJ) – Chair Janet A Betchkal MD (FL) William S Clifford MD (KS) Robert A Copeland Jr MD (Washington DC) Anna Luisa Di Lorenzo MD (MI) Sidney K Gicheru MD (TX) Michael L Gilbert MD (WA) Gary S Hirshfield MD (NY) Jeff S Maltzman MD (AZ) Thomas J McPhee MD (AZ) Lisa Nijm MD JD (IL) Andrew J Packer MD (CT) Diana R Shiba MD (CA) Woodford S Van Meter MD (KY) John (“Jack”) A Wells III MD (SC) Ex Officio Members Daniel J Briceland MD (AZ) Michael X Repka MD (MD) Russell Van Gelder MD PhD (WA) George A Williams MD (MI) **Surgical Scope Fund Committee Thomas A Graul MD (NE) – Chair Arezo Amirikia MD (MI) Matthew F Appenzeller MD (NC) Ronald A Braswell MD (MS) John P Holds MD (MO) Cecily A Lesko MD FACS (NJ) William (“Chip”) W Richardson II MD (KY) David E Vollman MD MBA (MO) Ex Officio Members Daniel J Briceland MD (AZ) Kurt F Heitman MD (SC) 9 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 not seem to be working well for his left eye. Everything up and to the left was blurred and lighter in color, he complained, for about a month. He visited the optometrist, where his refraction had not changed. He was seen later that week by a retina specialist, who noted 20/32 vision with correction O.U. and an otherwise entirely normal exam. Two weeks later, he had a visual field test that showed a temporal and superior defect in the left eye, with nonspecific change in the right. He was referred to neuroophthalmology and given an appointment with a VEP, about 6 weeks in the future. MRI was ordered by the optometrist and was pending insurance review and approval. Over the next 2 weeks, the patient felt increasing tired and achy and attributed these symptoms to stress. He also experienced a dull, daily headache with mild light sensitivity. The headache initially responded to over-the-counter ibuprofen treatment. Two days prior to his scheduled MRI, he experienced sudden, excruciating holocranial headache with photophobia. He had never before had such a severe headache. This occurred at work, and he was taken by his colleagues to the local emergency department for evaluation. A 37-year-old man with no significant past medical history presents with a chief complaint of “My head hurts for days on end.” The headache was strictly left-sided with a retrobulbar component. For the last 5 days, multiple headaches have occurred at the same times of day, each one lasting ~70 minutes, the first always waking him up at 4:30 a.m. With his headaches, the patient gets conjunctival injection and lacrimation of the affected side. When drinking alcohol or smoking a cigarette, the headache is exacerbated. The headaches are so severe that he is unable to sit still during one and paces the room, or even bangs his head against a wall to try and alleviate them. Evaluation reveals an anxious man, with normal acuity and color vision, and normal slitlamp and fundus exams. Motility and alternate cover test are normal. There is a 2-mm relative ptosis on the left. He has anisocoria, with right pupil 8 mm in the dark and 2 mm in the light; left eye 3 mm in dark, 1 mm in light, without afferent pupillary defect. There is dilation lag of the left eye with no vermiform movements of the pupil. Clinical Course and Outcome MRI brain with contrast showed a pituitary mass with hemorrhage. He was admitted for emergent neurosurgical intervention. He was found to have central hypoadrenalism, hypothyroidism, and possible diabetes insipidus, and his prolactin was mildly elevated. He awoke from surgery with markedly improved visual fields and 20/20 BCVA O.U., 11/11 Ishihara color plates, normal extraocular movement, and small relative afferent pupillary defect O.S. Clinical Course and Outcome Based on exam, it was felt that the patient’s anisocoria was due to autonomic dysfunction at the affected pupil. Two drops of 1.0% apraclonidine were administered to each eye. After 45 minutes, the right pupil remained unchanged, with constriction from 8 mm to 2 mm, but the left pupil size changed to 9 mm in the dark and 8 mm in the light. In addition, after apraclonidine, the left eyelid palpebral fissure increased and was now 1 mm more open than the right. At this point, further history was obtained, with the patient denying any recent cervical neck manipulation, trauma, or neck 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 verapamil, with sumatriptan as needed. Within 1 week, his headaches 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 for the past 3 months. She described the headache, which could involve the top of her head, as a stabbing pain lasting seconds and occasionally associated with a milder headache in between these episodes. On occasion she noted the pain over the right eye as well. She was in good health apart from the headaches. She had a motor vehicle accident without head trauma 1 year before the onset of symptoms. Ophthalmic examination revealed UCVA 20/20 in each eye with normal slitlamp examination (including gonioscopy) and funduscopy. MRI of the brain and orbits with contrast and magnetic resonance angiography of the head and neck without contrast showed no abnormalities. She was diagnosed with migraine and started on topiramate. Four weeks later she noted no improvement in the episodic pain. Palpation over the right trochlear region revealed no tenderness. Palpation over the occiput reproduced pain similar to her prior symptoms that radiated to the top of her head on the right side. Topiramate was discontinued and trigeminal neuralgia was considered. She started carbamazepine but had no relief of symptoms after 3 weeks. An injection of 0.5% bupivacaine in the region of the right greater occipital nerve, lateral and inferior to the external occipital protuberance, was performed. She reported relief of pain within minutes of the injection. The pain relief lasted 4 weeks before a mild discomfort in the same distribution recurred. Two months later a second injection largely relieved the symptoms, with some intermittent mild pain occurring once every few weeks. 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 complaint of headache, there are often immediate concerns for the physician. Is the pain attributable to eye disease? Does the pain arise from a headache syndrome? Is the symptom of pain evidence for some disease entity that could cause serious morbidity or even mortality? After all, the eye and periocular structures have sensory innervation from the trigeminal nerve; therefore pain in the head can arise from the eye, periorbita, or primary or secondary headache disorders. How can one quickly but thoroughly evaluate the patient and form a strategic plan, when appropriate, for additional diagnostic testing or therapeutic interventions? This presentation concentrates on simplifying the headache history and examination. History The goal of the history is to narrow the differential diagnosis and determine whether and what additional testing is indicated. The following are the typical questions that you should ask when a patient presents with a headache: 1. Do you have a history of headaches? If yes, then is this headache similar to those you have had in the past? It is not typical for a patient to see their ophthalmologist during their first or worst headache of their life. However, there might be a circumstance when you would be consulted on this type of patient in an emergency room. “First or worst” are red flags that may require urgent evaluation. If the headache is similar to prior headaches, without a change in frequency or severity, additional questions will help to define the differential diagnosis. 2. Is there a pattern to the headaches: are they associated with specific triggers or do they occur at a specific time or times 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 activities? What is the location and character of the headache? Does eye movement aggravate the pain? Migraine headaches are often associated with triggers that can include menses, food, alcohol, stress, and fatigue. Cluster headaches tend to occur recurrently at specific times of the day and may occur for one to many weeks followed by a headache-free interval. Eye movement often increases trochlear headache. 3. Do you have any associated symptoms with the headache? Specifically ask about nausea or vomiting, phonophobia, photophobia, and/or worsening with activity. These are all symptoms associated with migraine. Cluster headaches often are associated with nasal congestion or rhinorrhea, unilateral ptosis or lid edema, unilateral conjunctival injection, miosis, or facial sweating. In addition, patients often are restless during the headaches and prefer to keep moving, not still. The autonomic symptoms can also be seen with other classifications of the trigeminal autonomic cephalgias. Is there double vision? Microvascular ocular motor cranial mononeuropathies are often initially associated with pain or headache. Does the patient have a fever, rash, stiff neck, or discomfort with eye movements in association with the headache? Any infectious or meningeal signs such as fever, sweats, and/or neck pain worse with flexion must be promptly evaluated. 4. What is your past and current medical history? Specifically, is there a history of any cancer, autoimmune disease, or immunosuppression (medication induced or HIV)? Is it possible that the patient is pregnant? Is there a history of seizures? These would all be red flags that may require additional testing. 5. Do you have associated symptoms of weight loss, fevers, scalp pain, jaw or tongue claudication, and/or episodes of transient vision loss? Always remember giant cell arteritis in the differential diagnosis of individuals over the age of 50 with new-onset headache. Remember, if your suspicion is high for giant cell arteritis you must start high-dose steroids pending the full evaluation of the patient. 6. Are there any associated focal neurologic symptoms? These would all be red flags in the history that would require additional testing. 7. What medications are you taking? If the patient is using a migraine prophylactic agent such as topiramate, then failure to respond to the medicine may be the cause of the headache. Don’t forget, angle-closure glaucoma may occur in such patients and be misdiagnosed as headache! Overuse of over-the-counter analgesics may be associated with medication overuse headache or rebound headache. Clinical Exam The history has already helped you decide on the focus of the examination. However there are still a few remaining details that will help in determining the next steps. Diseases of the eye may cause pain that is interpreted by the patient as a headache. Common diseases that may have a subacute presentation include ocular surface disease such as dry eye or chronic exposure keratitis. Thyroid eye disease may present with ocular or orbital discomfort. Severe, acute, intermittent, or chronic pain may result also from keratitis, intraocular inflammation, angle-closure glaucoma, and orbital inflammatory diseases. Perform a thorough ocular and orbital examination. Specifically, examine the lids and orbit for signs of ptosis, proptosis, displacement of the globe, or lid retraction. Remember to palpate the trochlea to help identify cases of trochlear headache. Identify the BCVA and perform color vision screening and visual field testing. Examine the pupil carefully for anisocoria or for a relative afferent pupillary defect. Perform a motility evalu- 2015 Subspecialty Day | Neuro-Ophthalmology 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 neuroimaging 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. Section II: Eye Pain and Headache 13 14 Section II: Eye Pain and Headache “The light!! It hurts my eyes!!” Bradley J Katz MD C ase History and Exam A 45-year-old female presented with a chief complaint of light sensitivity. Her past medical history was unremarkable except for occasional “sinus headaches.” She reported no drug allergies and took no medications other than over-the-counter nonsteroidal anti-inflammatory drugs. Her symptoms had been present for the past 9 months and she’d consulted with two other eye doctors, who’d told her that her eyes were completely normal. Although she’d been “light sensitive” for most of her life, her symptoms were now to the point where she often wore sunglasses indoors. Her light sensitivity was beginning to interfere with her ability to work at her occupation in data entry. Her boss had refused to allow her to remove the fluorescent lights above her cubicle. Her eye examination was entirely normal. 2015 Subspecialty Day | Neuro-Ophthalmology Past medical history reveals controlled hypertension, benign prostatic hyperplasia, and hypothyroidism. Of note, he attributes his ptosis and facial asymmetry to childhood head injury sustained when kicked in the head by a cow. Current medications include doxazosin, lisinopril, levothyroxine, and finasteride. He has no known medication allergies. Social history and family history are unrevealing. On exam, Snellen visual acuity was 20/20 in each eye, without afferent pupillary defect (APD). Color perception by Ishihara plates was 8/11 in the right eye and 11/11 in the left eye. On dilated ophthalmoscopy, the right disc margin was slightly blurred, with cup-to-disc of 0.2 in each eye with otherwise normal fundi. External exam revealed 1-mm ptosis on the right and 2 mm of left ptosis, asymmetric facies, and a large scar on the left cheek. Ocular motility revealed decreased adduction of the right eye and the alignment measurements below: 6 XT 1 RHT 1 XT 2 XT 30 XT <1 RHT 6 RHT 6 RHT Clinical Course and Outcome Further questioning revealed that this patient had frequent headaches and that these headaches were often unilateral with a throbbing quality, increased light sensitivity, occasional sound sensitivity (“phonophobia”) and occasional nausea. She reported more than 15 headache days per month. This constellation of symptoms is consistent with a diagnosis of chronic migraine. She was using ibuprofen 800 mg once or twice a day, nearly every day, indicating that she may also be suffering from rebound headache. She was prescribed FL-41 tinted spectacles for indoor use and was scheduled to see a neurologist for prophylactic and acute treatment of migraine. 4 XT 10 RHT What is the most likely diagnosis? 1. 2. 3. 4. 5. Post-concussive headache with decompensated exophoria Myasthenia gravis Pupil-sparing aneurysmal third nerve palsy Temporal arteritis Complicated migraine Clinical Course and Outcome “It hurts when I talk, and this cough won’t go away.” Gabrielle R Bonhomme MD CASE History and Exam An 82-year-old male farmer presents with 2 weeks of intractable dry cough, intermittent blurred vision in his right eye, and transient, binocular, horizontal diplopia only on left gaze. He 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. Given his ptosis, transient binocular diplopia, blurred vision, and facial pain, the patient was admitted to the neurology service. Neuroimaging including brain MRI and MRA revealed normal intracranial vasculature and mild, diffuse small vessel ischemic changes attributable to age, and excluded stroke. Orbits were unremarkable. MRA of the neck excluded carotid dissection or stenosis. Acetylcholine receptor antibody panel was sent to 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. The patient was treated with IV methylprednisolone during inpatient stay, with 1 mg/kg prednisone taper directed by rheumatology. His cough, headaches, mouth pain, jaw claudication, and scalp tenderness quickly resolved on steroids. 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 way.” “I see two golf club heads when I 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 right gaze that first occurred 1 week prior to presentation. He denied decreased vision and ocular pain. His past medical history was remarkable for diabetes and hypertension. Medications included insulin and lisinopril. He consulted his local eye doctor, who diagnosed him with an “ischemic cranial nerve palsy.” Ophthalmologic examination: Visual acuity was 20/20 O.U. Confrontation visual fields were full O.U. External and slitlamp examination were normal. Ocular motility examination showed a complete abduction deficit O.D. Pupils were equal, reactive, without a relative afferent pupillary defect. Funduscopic examination was normal, with a flat optic disc in both eyes. Further diagnostic testing and treatment? A 57-year-old African American man presents to his ophthalmologist with a complaint of progressively worsening diplopia for the past 6 months. He reports that when he golfs, he gets double vision as he follows the ball in the air after he drives the ball. On exam, his acuity is 20/20 in both eyes. Slitlamp exam and funduscopic exam show mild cataracts but are otherwise unremarkable. He is noted to have a chin-up position. Exophthalmometry reveals 1 mm of proptosis on the left side. Motility exam shows a mild supraduction deficit in the left eye, otherwise full. On alternate cover testing, he has a 12 PD right hypertropia in primary gaze, increasing to 25 in upgaze and decreasing to 6 in downgaze. The deviation is fairly similar in right and left gazes and right and left head tilts. Clinical Course Clinical Course and Outcome Two weeks after presentation, the patient complained of right upper lid ptosis and anisocoria. Physical examination showed the previous complete right abduction deficit as well as right upper lid ptosis and mild limitations of adduction, elevation, and depression. Pupil examination showed anisocoria with a 3-mm pupil O.D. and a 4-mm pupil O.S. with no relative afferent pupillary defect. There was a right pupil dilation lag, and the amount of anisocoria increased with dim illumination. A diagnostic test was performed. The pupil examination showed Horner syndrome O.D. The combination of CN VI palsy, CN III palsy, and a Horner syndrome O.D. localized the pathology to the right cavernous sinus and mandated neuroimaging. An MRI of the brain with gadolinium showed a right cavernous sinus mass consistent with a meningioma. The patient did not elect to pursue further treatment. In summary, this is a case of binocular vertical diplopia with evidence of limited supraduction in one eye with associated mild proptosis. The differential diagnosis for this case includes mechanical and paretic causes of limited extraocular movements. A detailed history and review of systems is important to narrow down potential etiologies. The patient should be asked about a history of thyroid dysfunction, prior head or facial trauma, and prior eye surgery (particularly retinal detachment repair, scleral buckle placement, or previous retrobulbar block). A history of prior malignancy is also important to note. Congenital or traumatic fourth nerve palsies are the most common cause of acquired vertical deviations. Patients typically present with a hyperdeviation that worsens in the contralateral gaze and ipsilateral head tilt; however, longstanding deviations may show some spread of comitance. Symptoms are typically worst in activities requiring downgaze, such as reading or walking downstairs. On exam, a contralateral head tilt is often present, with fairly full extraocular movements and varying amounts of ipsilateral inferior oblique overaction. Vertical fusional amplitudes 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 commonly 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 thyroid dysfunction. Other findings consistent with TED can be helpful in confirming the diagnosis, which is typically a clinical one. Lid retraction, lid lag, temporal flare, lagophthalmos, limited abduction and resultant esotropia (due to medial rectus restriction), and proptosis can all be seen in TED, with lid lag being particularly specific. Elevation in IOP in upgaze and positive forced ductions can be signs of a restrictive strabismus, but are not specific for TED. For patients without a clear history of hyperthyroidism or lack of other findings on exam, orbital imaging can be helpful in ruling out other causes, including orbital masses and inflammatory diseases such as orbital myositis. A noncontrast orbital CT shows enlargement of the affected muscles, with sparing of the muscle tendons, with rare involvement of the lateral rectus muscle. Patients presenting with an exotropia and a diagnosis of TED should be evaluated for possible concurrent ocular myasthenia gravis, due to the increased association of the two diseases. Selected Readings 1. Harrad R. Management of strabismus in thyroid eye disease. Eye 2015; 29:234-237. 2. Peragallo JH, Velez FG, Demer JL, Pineles SL. Postoperative drift in patients with thyroid ophthalmopathy undergoing unilateral inferior rectus muscle recession. Strabismus. 2013; 21(1):23-28. 3. Volpe NJ, Mirza-George N, Binenbaum G. Surgical management of vertical ocular misalignment in thyroid eye disease using an adjustable suture technique. J AAPOS. 2012; 16(6):518-522. 4. Bothun ED, Scheurer RA, Harrison AR, Lee MS. Update on thyroid eye disease and management. Clin Ophthalmol. 2009; 3:543-551. 5. Chen VM, Dagi LR. Ocular misalignment in Graves disease may mimic that of superior oblique palsy. J Neuroophthalmol. 2008; 28(4):302-304. “Things are blurry and jumpy when I read.” Janet C Rucker MD C ase History and Exam A 29-year-old woman presented to her ophthalmologist reporting difficulty reading due to blurry vision. She explained that words seemed to “jump up and down” when she tried to read a book. She had first noticed this several months earlier. She occasionally noticed the jumping while watching television, but it was 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 Her medical history was significant for ovarian cancer that had been diagnosed and treated 3 years prior. She was statuspost hysterectomy, bilateral salpingo-oopherectomy, and chemotherapy with cisplatin and etoposide. Post-treatment, she developed gait difficulty with sensory loss in her feet that was attributed to chemotherapy-induced peripheral neuropathy. On exam, acuity was 20/30 O.U. Color vision, pupils, visual fields, and fundus were normal. Eye movement range was full. Vertical oscillations were seen in primary gaze that increased in lateral and downgaze and decreased in upgaze. It was characterized as a slow drift upward with a fast corrective jerk movement downwards. What would be the next step? Clinical Course and Outcome 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 between the nystagmus and her ovarian cancer history. The cancer history was several years ago, and she was closely followed by her gynecologic oncologist, who reported the patient’s cancer to be in remission. Brain metastasis from ovarian cancer is uncommon but must be considered. Thus, brain MRI with contrast would be the most appropriate initial diagnostic test. Other structural lesions that might be found on brain MRI and should also be in the differential diagnosis in a young woman with newonset DBN include a Chiari I malformation (a common cause of DBN), leptomeningeal enhancement (suggesting carcinoma or infection in the cerebrospinal fluid), and cerebellar or medullary demyelination or stroke. Brain MRI with contrast was normal. Patient was also sent by the ophthalmologist for a neurologic 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. Given the lack of an answer for a cerebellar process with DBN and ataxia, paraneoplastic cerebellar degeneration was highly suspect. Though isolated idiopathic DBN is quite common, the presence of ataxia and her history of ovarian cancer were quite concerning for a link between her exam findings and her cancer history. Lumbar puncture revealed normal cerebrospinal fluid, including negative cytology. Chest, abdomen, and pelvic CT scans were normal. Anti-GAD antibodies were negative, and thiamine level was normal. A paraneoplastic panel revealed anti-Yo antibodies in the serum. She was treated with a course of IVIg. Pelvic PET CT scan revealed lymph node enlargement suggestive of recurrent cancer. CT-guided biopsy confirmed recurrent ovarian cancer. Section III: Double Vision and Nystagmus 2015 Subspecialty Day | Neuro-Ophthalmology 17 Mini-Talk: Orbital Pulleys and Muscles Made Ridiculously Simple Joseph L Demer MD PhD determined by the relationship between its pulley and its scleral insertion. This mini-talk attempts humor in a valiant but probably futile effort to convince neuro-ophthalmologists that they should care about other things in the orbit besides nerves. All other approaches have so far failed, anyway. FDA Disclosure: Surface coils not approved by FDA were employed for some imaging studies. E. Peer pressure: Normal people have stereotypic pulley locations. But not everyone conforms. F. Orbital layers of the oblique EOMs translate the rectus pulleys in the coronal plane. Grant Support: USPHS National Eye Institute EY08313, and Research to Prevent Blindness. No financial conflict of interest exists. I. “I am shocked! Shocked!” Many of our 19th-century beliefs about the extraocular muscles (EOMs) are incorrect! A. EOMs are homogeneous structures that rotate the globe. D. EOMs follow straight paths from orbital apex to scleral insertion. C. Everyone has the same arrangement of EOMs. D. Abnormalities of EOMs are limited to underaction (paralysis or paresis), overaction, innervational miswiring, or stiffness. E. All important pathophysiology of EOMs can be diagnosed by clinical motility examination. F. Orbital connective tissues and EOM sleeves are not clinically very important. 1. The orbital layer of the inferior oblique inserts on the inferior rectus and lateral rectus pulleys. 2. The orbital layer of the superior oblique inserts on the superior oblique sheath posterior to the trochlea; the sheath travels through the trochlea and inserts on the superior rectus pulley. 3. In convergence, rectus pulley array excyclo rotates, due to orbital layers of oblique EOMs. G. Coordinated movements of the pulley’s ocular rotations account for Listing’s law of torsion and previously mysterious aspects of ocular kinematics. H. Pulley composition and structure are highly stereotypic. Pulleys are composed of dense, woven collagen, stiffened by elastin and incorporating smooth muscles having autonomic innervation. I. Pulleys reconfigure in situations not conforming to Listing’s law of ocular torsion. 1. Rectus pulley shirts torsionally with the eye during ocular torsion evoked by head tilting. 2. Rectus pulley array extorts during convergence, required for stereopsis. II. Amazing Revelations From 21st-Century Science A. Surface coil MRI of living human orbits has near microscopic resolution. B. Digital imaging of immuno- and histo-chemically stained whole human orbits permits 3-D reconstruction and correlation with in vivo MRI. IV. Duplicity of EOMs: Different Parts Do Different Things C. Classical physiologic data was equivocal and can be more satisfactorily reinterpreted in light of recent anatomical findings. III. Foolish EOMs don’t know their names. They just pull along paths defined by connective tissue pulleys. A. Rectus EOMs do not follow shortest, straight-line paths from orbital apex to scleral insertion. B. Connective tissue rings called pulleys are located between the globe equator and posterior pole that constrain EOM paths. C. Pulleys serve as the functional mechanical origins of the EOMs. D. Any rectus EOM can have horizontal, vertical, and torsional actions. Pulling direction of any EOM is A. Orbital layer 1. Contains 40%-50% of total muscle fibers 2. Inserts on the connective tissue pulley, not on the globe 3. Translates the pulley along EOM axis 4.Does not rotate the globe B. Global layer 1. Contains 50%-60% of total muscle fibers 2. Contiguous with the insertional tendon 3. Rotates the globe C. Global layer compartments 1. Separately controllable neuromuscular units 2. Apply force to different scleral insertion points along broad EOM tendons 18 Section III: Double Vision and Nystagmus 3. Differential function in inferior rectus, lateral rectus, medial rectus, and superior oblique (vertical vs. torsional) 2015 Subspecialty Day | Neuro-Ophthalmology VI. Nothing can protect pulleys from surgical exploitation by ophthalmologists who are in the know. A. Conventional strabismus surgical approaches expose the anterior parts of the pulleys. B. Suggestion: Handle pulley tissues conservatively, unless aim is to alter pulleys. C. Lost muscles retract into their pulleys, where they can generally be found. D. Efficacious pulley surgeries have been studied by MRI. V. Rebels With a Strabismus Cause Heterotopy (malpositioning) of rectus pulleys causes incomitant strabismus. A. Bad pulleys masquerade as cranial nerve palsies. A pulley out of place will cause rectus EOMs to pull in an oblique or torsional direction. B. Heterotopic pulleys can be diagnosed by appropriate orbital MRI or CT. C. Some pulleys are born for trouble. 1. Retroequatorial myopexy: Mechanism shown by MRI; interference of myopexy suture with the pulley. Stretching of the pulley suspension creates a mechanical restriction in the field of action of the operated EOM. 2. Augmented rectus transposition (Foster) 1. Congenital A pattern pulley heterotopy a. Superior location of lateral relative to medial rectus pulley in one or both orbits, so that the medial acts as a relative depression in adduction b. Or lateral location of inferior relative to superior rectus pulley in one or both orbits, so that the inferior rectus acts as an abductor in depression c. Both kinds of heterotopy will manifest overdepression in adduction and be confused clinically with “superior oblique overaction” 2. Congenital V pattern pulley heterotopy b. Produces large shifts in pulley position into the direction of the paralyzed EOM c. Benefits from extensive pulley dissection a. Inferior location of lateral relative to medial rectus pulley in one or both orbits, so that the medial rectus acts as a relative elevator in adduction 1. No scleral suturing is required. Just sew the pulley to the muscle belly. b. Or medial location of inferior relative to superior rectus pulley in one or both orbits, so that the inferior rectus acts as an adductor in depression 2. Modified approach works as well as conventional fadenoperation for acquired esotropia with high accommodative convergence-toaccommodation ratio. 3. Modified approach avoids risk of scleral perforation. c. Both kinds of heterotopy will manifest overelevation in adduction and be confused clinically with “inferior oblique overaction” 1. Sagging eye syndrome: Failure of the LR-SR band ligament may cause 15%-20% of adult acquired strabismus in U.S. practices. a. More effective than full tendon width rectus transfer for paralytic strabismus E. Posterior fixation (“fadenoperation”) works by creating hindrance to posterior pulley shift during EOM contraction. F. Conventional surgery works in sagging eye syndrome. D. Some pulleys have trouble thrust upon them. a. Age-related distance esotropia (ARDE): Bilaterally symmetrical failure causes symmetrical lateral rectus sag, converting some lateral rectus force from abduction to infraduction. b. Asymmetrical lateral rectus sag causes hypotropia and excyclotropia ipsilateral to the greater sag. This may resemble superior oblique palsy, except that excyclotropia is in the lower eye. 2. Heavy eye syndrome: Large angle esotropia and ipsilateral hypotropia associated with high axial myopia. The lateral rectus pulley slips under the globe, converting the lateral rectus from an abductor to a depressor. 1. “All-in” medial rectus recession works well for ARDE. Hint: Do not be timid. Recess both medial rectus muscle in nearly every patient, and recess for a target angle twice the largest ET measured in any distance gaze position. Check convergence amplitudes first, consider topical anesthesia. 2. Partial rectus tenotomy under topical anesthesia works well for cyclovertical strabismus. Selected Readings (Hidden in Plain Sight All This Time!) 1. Demer JL, Miller JM, Poukens V, Vinters HV, Glasgow B. Evidence for fibromuscular pulleys of the recti extraocular muscles. Invest Ophthalmol Vis Sci. 1995; 36:1125-1136. 2. Porter JD, Poukens V, Baker RS, Demer JL. Structure-function correlations in the human medial rectus extraocular muscle pulley. Invest Ophthalmol Vis Sci. 1996; 37:468-472. 2015 Subspecialty Day | Neuro-Ophthalmology Section III: Double Vision and Nystagmus 19 3. Clark RA, Miller JM, Demer JL. Location and stability of rectus muscle pulleys: muscle paths as a function of gaze. Invest Ophthalmol Vis Sci. 1997; 38:227-240. 22. Demer JL, Kono R, Wright W. Magnetic resonance imaging of human extraocular muscles in convergence. J Neurophysiol .2003; 89:2072-2085. 4. Demer JL, Poukens V, Miller JM, Micevych P. Innervation of extraocular pulley smooth muscle in monkey and human. Invest Ophthalmol Vis Sci. 1997; 38:1774-1785. 23. Demer JL, Oh SY, Clark RA, Poukens V. Evidence for a pulley of the inferior oblique muscle. Invest Ophthalmol Vis Sci. 2003; 44:3856-3865. 5. Clark RA, Miller JM, Rosenbaum AL, Demer JL. Heterotopic rectus muscle pulleys or oblique muscle dysfunction? J AAPOS. 1998; 2:17-25. 24. Demer JL. Ocular kinematics, vergence, and orbital mechanics. Strabismus 2003; 11:49-57. 6. Demer JL, Clark RA, Miller JM. Role of orbital connective tissue in the pathogenesis of strabismus. Am Orthoptic J. 1998; 48:56-64. 25. Demer JL. Pivotal role of orbital connective tissues in binocular alignment and strabismus. The Friedenwald Lecture. Invest Ophthalmol Vis Sci. 2004; 45:729-738. 7. Clark RA, Isenberg SJ, Rosenbaum AL, Demer JL. Posterior fixation sutures: a revised mechanical explanation for the fadenoperation based on rectus extraocular muscle pulleys. Am J Ophthalmol. 1999; 128:702-714. 26. Clark RA, Ariyasu R, Demer JL. Medial rectus pulley posterior fixation is as effective as scleral posterior fixation for acquired esotropia with a high AC/A ratio. Am J Ophthalmol. 2004; 137:10261033. 8. Demer JL, Miller JM. Orbital imaging in strabismus surgery. In: Rosenbaum AL and Santiago P., eds. Advanced Strabismus Surgery. New York: Mosby; 1999:84-98. 27. Pirouzian A, Goldberg RA, Demer JL. Inferior rectus pulley hindrance: orbital imaging mechanism of restrictive hypertropia following lower lid surgery. J AAPOS. 2004; 8:338-344. 9. Demer JL, Clark RA, Miller JM. Heterotopy of extraocular muscle pulleys causes incomitant strabismus. In: Lennerstrand G, ed. Advances in Strabismology. Amsterdam: Swets; 1999: 91-94. 28. Clark RA, Ariyasu R, Demer JL. Medial rectus pulley posterior fixation: a novel technique to augment recession. J AAPOS. 2004; 8:451-456. 10. Demer JL, Oh SY, Poukens V. Evidence for active control of rectus extraocular muscle pulleys. Invest Ophthalmol Vis Sci. 2000; 41(6):1280-1290. 29. Kono R, Poukens V, Demer JL. Superior oblique muscle layers in monkeys and humans. Invest Ophthalmol Vis Sci. 2004; 46:27902799. 11. Demer JL. Extraocular muscles. In: Jaeger EA and Tasman PR., eds. Clinical Ophthalmology. Philadelphia: Lippincott Williams and Wilkins; 2000, vol. 1, ch. 1. 30. Demer JL, Clark RA. Magnetic resonance imaging of human extraocular muscles during static ocular counter-rolling. J Neurophysiol. 2005; 94:3292-3302. 12. Clark RA, Miller JM, Demer JL. Three-dimensional location of human rectus pulleys by path inflections in secondary gaze positions. Invest Ophthalmol Vis Sci. 2000; 41:3787-3797. 31. Demer JL. Current concepts of mechanical and neural factors in ocular motility. Curr Opin Neurol. 2006; 19:4-13. 13. Oh SY, Poukens V, Demer JL. Quantitative analysis of extraocular muscle layers in monkey and human. Invest Ophthalmol Vis Sci. 2001; 42:10-16. 14. Clark RA, Demer JL. Rectus extraocular muscle pulley displacement after surgical transposition and posterior fixation for treatment of paralytic strabismus. Am J Ophthalmol. 2002; 133:119128. 15. Demer JL. The orbital pulley system: a revolution in concepts of orbital anatomy. Ann NY Acad Sci. 2002; 956:17-32. 16. Oh SY, Clark RA, Velez F, Rosenbaum AL, Demer JL. Incomitant strabismus associated with instability of rectus pulleys. Invest Ophthalmol Vis Sci. 2002; 43:2169-2178. 17. Kono R, Clark RA, Demer JL. Active pulleys: magnetic resonance imaging of rectus muscle paths in tertiary gazes. Invest Ophthalmol Vis Sci. 2002; 43:2179-2188. 18. Kono R, Poukens V, Demer JL. Quantitative analysis of the structure of the human extraocular muscle pulley system. Invest Ophthalmol Vis Sci. 2002; 43:2923-2932. 19. Clark RA, Demer JL. Effect of aging on human rectus extraocular muscle paths demonstrated by magnetic resonance imaging. Am J Ophthalmol. 2002; 134:872-878. 20. Demer JL. A 12 year, prospective study of extraocular muscle imaging in complex strabismus. J AAPOS. 2003; 6: 337-47. 21. Miller JM, Demer JL, Poukens V, Pavlowski DS, Nguyen HN, Rossi EA. Extraocular connective tissue architecture. J Vision. 2003; 2:12-23. 32. Demer JL. Gilles Lecture: Ocular motility in a time of paradigm shift. Clin Experiment Ophthalmol. 2006; 34:822-826. 33. Demer JL. Mechanics of the orbita. Dev Ophthalmol. 2007; 40:132-157. 34. Lim KH, Poukens V, Demer JL. Fascicular specialization in human and monkey rectus muscles: evidence for structural independence of global and orbital layers. Invest Ophthalmol Vis Sci. 2007; 48:3089-3097. 35. Kono R, Okanobu H, Ohtsuki H, Demer JL. Displacement of the rectus muscle pulleys simulating superior oblique palsy. Japn J Ophthalmol. 2008; 52:36-43. 36. Demer JL. Inflection in inactive lateral rectus muscle: evidence suggesting focal mechanical effects of connective tissues. Invest Ophthalmol Vis Sci. 2008; 49:4858-4864. 37. Demer JL, Clark RA, Crane BT, Tian JR, Narasimhan A, Karim S. Functional anatomy of the extraocular muscles during vergence. Prog Brain Res. 2008; 171:21-28. 38. Clark RA, Demer JL. Posterior inflection of weakened lateral rectus path: connective tissue factors reduce response to lateral rectus recession. Am J Ophthalmol. 2009; 147:127-133. 39. Rutar T, Demer JL. “Heavy eye syndrome” in the absence of high myopia: a connective tissue degeneration in elderly strabismic patients. J AAPOS. 2009; 13:36-44. 40. da Silva Costa RM, Kung J, Poukens V, Yoo L, Tychsen L, Demer JL. Intramuscular innervation of primate extraocular muscles: unique compartmentalization in horizontal recti. Invest Ophthalmol Vis Sci. 2011; 52:2830-2836. 41. Demer JL, Dusyanth A. T2 fast spin echo magnetic resonance imaging 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 extraocular muscles in head tilt dependent hypertropia. Invest Ophthalmol Vis Sci. 2011; 52:3023-3031. 49. Clark RA, Demer JL. Differential lateral rectus compartmental contraction during ocular counter-rolling. Invest Ophthalmol Vis Sci. 2012; 53:2887-2896. 43. Demer JL, Clark RA, da Silva Costa RM, Clark RA, Kung J, Yoo L. Expanding repertoire in the oculomotor periphery: selective compartmental function in rectus extraocular muscles. Ann NY Acad Sci. 2011; 1233:8-16. 50. Chaudhuri Z, Demer JL. Sagging eye syndrome: connective tissue involution causes horizontal and vertical strabismus in older patients. JAMA Ophthalmol. 2013; 131:619-625. 44. Wabulembo G, Demer JL. Long term outcome of medial rectus recession and pulley posterior fixation in esotropia with high AC/A ratio. Strabismus 2012; 20:115-120. 45. Chaudhuri Z, Demer JL. Medial rectus recession is as effective as lateral rectus resection in divergence paralysis esotropia. Arch Ophthalmol. 2012; 130:1280-1284. 46. Pineles SL, Laursen J, Goldberg RA, Demer JL, Velez FG. Function of transected or avulsed rectus muscles following recovery using an anterior orbitotomy approach. J AAPOS. 2012; 16:336-341. 47. Clark RA, Demer JL. Functional morphometry of horizontal rectus extraocular muscles during ocular duction. Invest Ophthalmol Vis Sci. 2012; 53:7375-7379. 48. Shin A, Yoo L, Chaudhuri Z, Demer JL. Independent passive mechanical behavior of bovine extraocular muscle compartments. Invest Ophthalmol Vis Sci. 2012; 53:8414-8423. 51. Demer JL, Clark RA. Differential compartmental function of medial rectus muscle during conjugate and converged ocular adduction. J Neurophysiol. 2014; 112(4):845-855. 52. Demer JL. The Apt Lecture: Connective tissues reflect different mechanisms of strabismus over the life span. J AAPOS. 2014; 18:309-315. 53. Demer JL. Compartmentalization of extraocular muscle function. Eye (Lond.) 2014; 29:157-162. 54. Shin A, Yoo LY, Demer JL. Independent active contraction of extraocular muscle compartments. Invest Ophthalmol Vis Sci. 2015; 56:199-206. 55. Demer JL, Clark RA. Magnetic resonance imaging demonstrates compartmental muscle mechanisms of human vertical fusional vergence. J Neurophysiol. 2015; 13:2150-2163. 56. Peragallo JH, Pineles SL, Demer JL. Recent advances clarifying the etiologies of strabismus. J Neuroophthalmol. 2015; 35:185-193. 2015 Subspecialty Day | Neuro-Ophthalmology “Words run together on the TV.” Kimberly M Winges MD C ase Clinical History and Exam A 68-year-old woman was referred by optometry for recurrent episodes of binocular horizontal diplopia that started 3 years ago and worsened over the last few months. She described words running together in the captions on the television screen, resolved by closing either eye. Diplopia was present only at distance, never at near, and it was not associated with fatigue or change in position. She denied new medications, lid drooping, trouble with speech or ambulation, dizziness, headache, jaw claudication, transient visual loss, or childhood strabismus. Her past medical history was remarkable for pseudophakia O.U. and hypothyroid disease. Eye exam revealed 20/20 BCVA O.U., normal near stereoacuity (8/9 circles by Titmus test), full confrontation visual fields, no relative afferent pupillary defect, and no proptosis or ptosis of either eye. Slitlamp biomicroscopy and dilated exams were healthy, showing centered IOLs O.U. Extraocular motility testing revealed 5 PD of esotropia in primary gaze, which increased to 8 PD in right and left gaze. Maddox rod testing did not elicit a vertical deviation or ocular torsion. She was orthophoric at near. Ductions were full, with normal saccades, slightly choppy pursuit, and intact vestibulo-ocular reflex testing. What would you do next? 1. Observe and place Fresnel prism on her glasses 2. Order ESR and CRP and start empiric prednisone treatment 3. Order MRI brain w/wo contrast 4. Order TSH and noncontrast CT orbit Clinical Course and Outcome In summary, this is a case of adult-onset intermittent, binocular, horizontal diplopia, with exam revealing a relatively comitant esotropia at distance, full ductions, and orthophoria at near. With an otherwise normal eye exam apart from pseudophakia, the main differential diagnosis includes divergence insufficiency (DI) or subtle bilateral CN VI palsies. In this patient, the full ductions and normal saccade velocity made 6th nerve palsy less likely. Also, there were no other signs or symptoms of increased intracranial pressure, which can cause bilateral CN VI palsy due to downward displacement of the brain over the 6th nerves 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 disease, which is usually accompanied by other suggestive ocular findings. While nomenclature may vary, the term “divergence insufficiency” (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 targets. 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- Section III: Double Vision and Nystagmus 21 ated with spinocerebellar ataxia, progressive supranuclear palsy, brainstem stroke, cerebellar and skull-based lesions, or head trauma. This phenomenon has also been reported in patients with increased intracranial pressure, where the distinction 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 found to have downbeat nystagmus and ataxic, wide-based gait. Her mother had developed similar symptoms without diagnosis years prior. Brain MRI showed cerebellar atrophy, and she was eventually diagnosed with spinocerebellar atrophy. Workup of DI should be based upon careful attention to any signs of cranial nerve palsy or historical/exam details suggesting a neurologic cause (such as ataxia or presence of nystagmus, for example). When appropriate, neuroimaging can rule out brainstem or other skull base lesions. Lab testing should be tailored to the history and exam findings that invoke suspicion of other sources of diplopia, such as myasthenia gravis, thyroid disease, or temporal arteritis. When no neurologic cause is suspected or found, DI is considered primary or idiopathic. In some cases of age-related distance esotropia, mechanical changes in the orbit can be shown on highresolution MRI that cause inferior displacement of the lateral rectus and breaking of the lateral rectus-superior rectus band. These involutional changes cause esotropia and hypotropia, or the sagging eye syndrome, commonly associated with blepharoptosis and cyclovertical strabismus. This more recently recognized syndrome may be a source of DI in the elderly. 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 to alleviate her diplopia in distance spectacles. References 1. Liu GT, Volpe NJ, Galetta SL. Eye movement disorders: third, fourth, and sixth nerve palsies and other causes of diplopia and ocular misalignment. In: Neuro-ophthalmology: Diagnosis and Management, 2nd ed. New York: Saunders Elsevier; 2010:491-550. 2. Kline LB, Foroozan R. Supranuclear and internuclear gaze pathways. In: Neuro-Ophthalmology Review Manual, 7th ed. Thorofare, NJ: SLACK Inc.; 2013:45-72. 3. Jacobson DJ. Divergence insufficiency revisited: natural history of idiopathic cases and neurologic associations. Arch Ophthalmol. 2000; 118:1237-1241. 4. Chaudhuri Z, Demer JL. Sagging eye syndrome: connective tissue involution as a cause of horizontal and vertical strabismus in older patients. JAMA Ophthalmol. 2013; 131(5):619-625. 5. Mittelman D. Age-related distance esotropia. J AAPOS. 2006; 10(3):212-213. 22 Section III: Double Vision and Nystagmus “I see double when I get tired.” Marc J Dinkin MD C ase 2015 Subspecialty Day | Neuro-Ophthalmology “I see double after my cataract surgery.” Stacy L Pineles MD C ase History and Exam A 45-year-old female photo editor with a medical history of hypertension and high cholesterol presented with double vision when tired. Eleven months before presentation, her left eye began deviating outward intermittently, especially when tired and at the end of a long work day. This was soon followed by intermittent binocular vertical diplopia, worse in downgaze and worse when tired and after a glass of wine. An MRI of brain and orbits was obtained by her primary medical doctor and was normal. Patient was diagnosed by an ophthalmologist as experiencing a breakdown of congenital strabismus and offered corrective surgery. She opted instead to patch one eye and seek another opinion and presented for neuro-ophthalmic consultation. She endorsed bouts of left upper eyelid ptosis, lasting a few weeks intermittently over the last year. Family history was significant for diabetes in both parents. 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 20/20 in left eye. Pupils were equal in the dark, but in the light, the left pupil was 1 mm larger. Intraocular pressures, confrontational visual fields, and funduscopy were unremarkable. Extraocular movements appeared full, but cross-cover testing demonstrated 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 and to the left, as well as in right head tilt. Saccades were slowed in the horizontal direction. There was left ptosis and Hertel exophthalmometry revealed measurements of 23 cm on the right and 21 cm on the left. Clinical Course Cogan lid twitch sign was not detected, but there was significant fatigability with worsening of left ptosis after 1 minute of upgaze. Enhanced ptosis (curtaining) was present bilaterally. The remaining general neurological examination was normal, including testing for fatigability of the deltoids and ability to count to 30 in one breath. After 20 minutes of rest, the palpebral fissure and marginal reflex distance became equal at 10 and 5 mm, respectively, in both eyes. Laboratory testing revealed elevated binding, blocking, and modulating acetylcholine receptor antibodies: 68.0 nmol/L (normal: 0.05 nmol/L), 45% and 83%, respectively. MRI of the chest demonstrated a minimally enhancing soft tissue mass of the thymus measuring 8.4x3.5 cm. Computed tomography revealed calcification of the mass. A robotic thymectomy was performed, and the mediastinal mass contained both thymic tissue and amyloid. The patient was treated with oral steroids for 3 months and experienced complete resolution of ptosis and diplopia. History and Exam A 66-year-old man presents with decreasing vision in both eyes (left more than right) for about 3 years. He also notices glare at night. His past ocular history is significant for a history of “lazy eye” during childhood. He thinks he wore glasses and maybe patched one eye during childhood to correct his lazy eye. He does not notice any diplopia at this time. The remainder of his past medical, surgical, social, and family history was noncontributory. On examination, his BCVA is 20/40 O.D. and 20/60 O.S. His refraction is +2.50 O.U. He has a small esotropia. His slitlamp examination is normal except for 2+NS cataract O.D. and 2+NS/2+PSC O.S. His dilated fundus examination is normal. He underwent uncomplicated cataract surgery in the left eye and on postoperative Day 1, he began to notice binocular diplopia. At that time, his BCVA was 20/40 O.D. and 20/25 O.S. What is the most likely etiology of his double vision? 1. 2. 3. 4. Extraocular muscle contracture after retrobulbar injection Unmasked esotropia from thyroid eye disease Fixation switch diplopia Monocular diplopia due to induced astigmatism Clinical Course and Outcome On further examination, the patient was found to have refractive errors of +2.50 O.D. and +0.50 O.S. His motility examination demonstrated a comitant esotropia of 6 PD at distance and near. 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 prism glasses and then underwent cataract surgery in his right eye. He continued to need the prism but could be weaned down from 6 PD to 2 PD to no prism over a period of a few months. As he began to fixate with his right eye, the diplopia resolved despite a residual esotropia of 4 PD. The differential diagnosis for binocular diplopia after cataract surgery typically includes anesthetic myotoxicity from a retrobulbar injection, pre-existing strabismus masked by the cataract (due to thyroid eye disease, myasthenia gravis, other forms of strabismus), central disruption of fusion, optic aberrations, or disorders unique to a history of amblyopia such as elimination of suppression in the amblyopic eye due to a long-standing cataract, a change in the angle of strabismus leading to a drift outside of the suppression scotoma, or fixation switch diplopia. This patient was diagnosed with fixation switch diplopia because it was clear that his diplopia began after his fixation was switched from the right eye to the left eye. In this case, the patient’s dominant eye (O.D.) had poorer vision after the left eye underwent cataract surgery and was corrected to 20/25. Once the right eye was corrected to 20/20, the patient was able to regain fixation with the dominant eye and his diplopia resolved as his left eye vision was moved back into his appropriate facultative suppression scotoma. Section IV: Test Interpretation 2015 Subspecialty Day | Neuro-Ophthalmology 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 with a 1-year history of blurred vision in both eyes. She had a history of hypertension, which was well controlled, and was otherwise healthy. Family history was notable for a sister with glaucoma but was otherwise unremarkable. She did not smoke and only drank alcohol socially. She was using amlodipine for blood pressure control and zolpidem for sleep as needed. She had noticed more difficulty with reading and driving, particularly with left turns and left lane changes. On initial examination, BCVA was 20/30 O.D., 20/25 O.S., attributed to mild cataracts. Pupils were normal, with no relative afferent pupillary defect noted. IOP was 19 O.D., 20 O.S. Fundus examination showed flat optic discs, cup-to-disc 0.5 O.D., 0.45 O.S., with some thinning of the temporal rim. The remainder of the examination was unremarkable. Humphrey visual fields were performed. These were interpreted as showing an inferior altitudinal defect in the right eye and a superior arcuate defect in the left eye. The working diagnosis at that time was “normal-tension glaucoma vs. previous nonarteritic ischemic optic neuropathy (NAION).” The patient missed a follow-up appointment and returned nearly 9 months later. Visual acuity was now 20/40 O.U. Her fundus examination showed possible neuroretinal rim pallor O.U. Repeat Humphrey visual fields showed worsened field loss. A previously healthy 24-year-old woman experienced sudden loss of vision of the left eye while jogging on a treadmill. Within 45 minutes the vision improved but did not return to normal. She denied eye pain, headache, or any other systemic or neurological symptoms. The only medication she was taking was ethinyl estradiol/norgestrel (oral contraceptive pills). She did not smoke and had only an occasional alcoholic beverage. Family history was unremarkable. The patient presented to a local emergency room and was evaluated by an ophthalmologist and admitted to the hospital for management of the visual loss. Patient reports that she had blood work, cranial MRI, and transesophageal echocardiogram that were all reported to be negative or normal. She was discharged from the hospital after 3 days and referred to a local retina specialist. On her initial follow-up examination, visual acuity was noted to be 20/20 O.D. and hand motions O.S. An intravenous fluorescein angiogram was interpreted as showing choroidal ischemia O.S. Approximately 3 months after the onset of visual loss, vision was 5/200 O.S. with superior optic nerve pallor, resulting in a referral to the neuro-ophthalmology service. Clinical Course and Outcome The patient was referred to neuro-ophthalmology. The examination was unchanged, but the field defect raised concern for a chiasmal lesion. MRI of the brain and orbits with and without gadolinium was performed. This demonstrated a large, homogeneously enhancing mass compressing the optic chiasm and the right intracranial optic nerve, most compatible with suprasellar meningioma. She underwent surgical resection of the tumor and did well postoperatively, with partial recovery of field and visual acuity. Clinical Course and Outcome 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. and 20/30 O.S. Color vision with the Ishihara pseudochromatic plates was 10/10 O.D. and 7.5/10 O.S. There was a left relative afferent pupillary defect. Orbital, ocular motility, IOP, and slitlamp biomicroscopy examinations were all normal. Funduscopic examination of the right eye was normal. In the left eye, the superior pole of the optic nerve was pale, with narrowing of the superotemporal arcade vessel. Automated perimetry demonstrated a dense inferior altitudinal defect O.S. OCT retinal nerve fiber layer thickness was normal O.D. (96 µm) and thin superotemporally 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 “I can’t get cocaine drops in my office!” Heather E Moss MD PhD C ase History and Exam A 67-year-old man in excellent health presented for evaluation of 1 month of right eyelid drooping. He thought it got better in the evening. He denied diplopia or change in vision. He had not had headaches, dyspnea, dysarthria, or dysphagia. On review of systems he noted right shoulder pain. He was not taking any medications. He smoked 3 cigarettes each day. He had a history of cocaine use, last 6 months prior to evaluation. On examination, visual acuity was 20/20 with each eye. Ductions were full. The right pupil was 1 mm smaller than the left pupil. There was no relative afferent pupillary defect. There was 2 mm of relative ptosis of the right eye. Anterior and posterior ophthalmoscopic exams were unremarkable. What would you do next? • • • • MRI scan Send to emergency department Refer to neuro-ophthalmology Do further in office testing/examination Clinical Course and Outcome Unilateral ptosis and miosis are concerning for a diagnosis of Horner syndrome. Other diagnostic considerations include concurrent causes of isolated ptosis (eg, aponeurotic, myasthenia gravis, third nerve palsy) and anisocoria (eg, physiologic, tonic pupil, third nerve palsy). Additional clinical examination can quickly refine the diagnosis. Further diagnostic information regarding anisocoria can be easily obtained by comparing the relative anisocoria in light and dark environments. In this case, detailed pupil exam revealed that the right pupil was 1 mm smaller than the left pupil with the room lights on and 1.5 mm smaller than the left pupil with the room lights off. This suggested that the right eye was not dilating adequately due to sympathetic dysfunction. Further diagnostic information regarding ptosis can be 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 without curtain, twitch, or fatigue. This could be consistent with aponeurotic ptosis or Müller muscle weakness due to sympathetic 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 In any case of ptosis and/or anisocoria, further review of systems and examination can help to refine the differential diagnosis. Though not seen in our patient, ocular misalignment could point toward third nerve palsy, myasthenia gravis, or cavernous sinus syndrome. Accompanying numbness, weakness, or coordination 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, cervical spine, or neck. His cocaine history, though remote, suggested vascular etiologies. In this case the anisocoria worse in the dark and ptosis with normal levator function were sufficient to clinically diagnose Horner syndrome, and workup was initiated to identify a causal etiology. If the exam is equivocal or if there are contraindications to imaging, eye drop testing can be used to confirm a Horner syndrome diagnosis. Cocaine drops act presynaptically and cause less dilation of a pupil with sympathetic dysfunction than of a pupil without sympathetic dysfunction. Apraclonidine, which is more readily available than cocaine, acts postsynaptically to cause more dilation of a pupil with sympathetic dysfunction than of a pupil without sympathetic dysfunction. Literature suggests that both tests have similar sensitivity and sensitivity for Horner syndrome. Based on the mechanisms of action, cocaine is theoretically more sensitive than apraclonidine in the hyperacute setting, though reports suggest that this does not limit its use in clinical practice. In our patient, apraclonidine testing had been used by the referring provider, who reported that 30 minutes following instillation of 1 gtt. of 0.5% apraclonidine in each eye, the right pupil was 1 mm larger than the left. This confirmed a diagnosis of right Horner syndrome. If there is a known causal explanation (eg, recent carotid instrumentation, known recent lateral medullary stroke), then further evaluation may not be needed. However, this was not the case with our patient, so imaging was necessary to screen for etiologies requiring treatment. Complete evaluation of the sympathetic chain includes brain imaging (MRI, not CT), neck imaging (MRI), carotid angiographic imaging (CTA or MRA, not carotid ultrasound), and chest imaging (CT or MRI, not chest x-ray), which can be refined or staged based on accompanying signs and symptoms. Important etiologies requiring treatment include brainstem stroke or tumor, Pancoast tumor in the lung apex, carotid pathology such as dissection, cavernous sinus pathology such as tumor, or orbital process. In our case, MRI of the brain and neck, MRA neck, and CT chest with contrast were obtained. The chest CT showed a right lung apex mass. Biopsy was diagnostic of small cell lung cancer. Section IV: Test Interpretation 2015 Subspecialty Day | Neuro-Ophthalmology Mini-Talk: Bias in Testing—Do I Only Find What I Thought Was There? Harold E Shaw Jr MD NOTES 25 26 Section IV: Test Interpretation “The MRI is abnormal; now what?” Fiona E Costello MD C ase 2015 Subspecialty Day | Neuro-Ophthalmology Everyone’s ESR Is High: Who Needs a Biopsy? Todd Alan Goodglick C ase History and Exam History A 30-year-old woman with recent headaches is admitted after 2 generalized tonic-clonic seizures. Her comorbidities include Crohn disease, for which she recently initiated treatment with infliximab. The patient stands 5 feet tall and weighs 260 lbs. Over the past 4 weeks she has experienced a 30-lb. weight loss secondary to bloody diarrhea from active inflammatory bowel disease. She describes a week-long history of blurred vision in both eyes. She describes episodes of visual dimming in one or both eyes that is often triggered by rapid position changes and hears a pulsing “heartbeat in her ears.” She denies diplopia. Examination Visual acuity is 20/100 in the right eye and 20/80 in the left eye. Pupils measure 4 mm in darkness and constrict to 3 mm in bright light with no relative afferent pupillary defect. The patient is able to read 3/6 Hardy-Rand-Rittler pseudoisochromatic plates with each eye. Ocular motility and external ocular examination are normal. The visual field testing and fundus examination are depicted in Figures 1 and 2. The patient undergoes a cranial MRI scan with venography, which demonstrates a partially empty sella, bilateral flattening of the globes, and tortuosity of the optic nerve sheaths. Initially, the MR venogram is reported as normal. History and Exam Fifty-nine-year-old white woman referred for variable headache on her left side for 3 months, without association to activity or position, pain around the ears and in throat. She specifically denies jaw claudication. She also notes 2 episodes, 2 and 3 weeks ago, of graying out of part of her peripheral vision in her left eye, but it only lasted about a minute so she didn’t seek help. Her internist has previously obtained a noncontrast MRI of the head and carotid Doppler study, which were normal. Patient’s past medical history includes type 2 diabetes mellitus, hypertension, and generalized arthritis presently in a flareup, including the neck, which she attributes the headache to. She was diagnosed with pneumonia 3 weeks ago, associated with fevers and mild congestive heart failure. Her visual acuities were 20/25 O.D., 20/30 O.S. The rest of her examination was normal. Clinical Course and Outcome Below are possible laboratory results: Sed rate C-reactive protein 1 2 3 4 22 35 60 60 0.5 5 0.5 5 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, transient 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.” Marie D Acierno MD Final Diagnosis This young man has unilateral optic neuritis. Teaching Points Optic neuritis is an acute inflammatory disorder of the optic nerve commonly associated with multiple sclerosis. It is manifest by acute, unilateral visual loss, eye pain, typically with eye movement, decreased color and/or decreased contrast, visual field defect, and a relative afferent pupillary defect. Ninety-two percent of patients have accompanying pain. Sixty-five percent of patients have a normal appearing optic nerve, reflecting retrobulbar disease, while 35% have optic disc edema. Our patient presented with optic disc edema (rather diffuse / severe without hemorrhages), a less common presentation for acute, isolated optic neuritis. If a patient presents with optic disc edema, it may be necessary to re-examine the patient in several days to assess for development of macular exudates. This finding establishes the diagnosis of neuroretinitis, which is not associated with demyelinating disease and therefore does not warrant neuroimaging. Sarcoid can also present as a typical optic neuritis, usually with optic disc involvement. Visual recovery varies for sarcoid optic neuritis, but it often does not improve without steroid therapy. One should definitely consider Leber hereditary optic neuropathy (LHON) in such a clinical presentation. LHON may occur in both men and women, but it is more common in young adult males. Patients with LHON may present with a normal-appearing disc in the affected eye or with mild disc swelling with peripapillary telangiectasia. LHON is a painless visual loss resulting in a dense central scotoma in the affected eye. Only those LHON patients with specific mitochondrial mutations may experience partial or complete visual recovery after months or years. Patients will usually acquire bilateral simultaneous visual loss in weeks to months in the contralateral eye. The risk of developing MS following an acute optic neuritis is lower for those patients with severe optic disc swelling with hemorrhages or a macular star, absence of pain, vision reduced to no light perception, and in males. In a typical presentation of optic neuritis, blood laboratory testing and lumbar puncture are not indicated. If the clinical course is unusual in any way, such as prolonged pain, lack of visual recovery within 4 to 6 weeks, recurrence within 2 months, or manifestation of other clinical findings, the presentation is considered atypical and a workup is pursued accordingly. Optic neuritis may be the first clinical sign of MS or it may occur in a patient with the established diagnosis of MS. Our patient’s MRI orbit imaging study demonstrates left optic nerve enhancement, which is helpful but not necessary for the diagnosis of optic neuritis. Contrast-enhanced imaging with fat suppression technique allows optimal views of the optic nerves. MRI brain/orbit imaging study with gadolinium should be considered in all patients with optic neuritis to assess the risk for MS. MS demyelinating plaques can be found throughout the brain but have a predilection for the periventricular white matter region in an ovoid configuration perpendicular to the periventricular region and lateral borders of the corpus callosum. The overall 15-year risk of developing MS after optic neuritis is 50% based on clinical criteria. However, the risk can be further refined. In the absence of demyelinating lesions, the risk is low, at 25%, while the risk is 72% when lesions are present. If the clinical presentation has the typical features of an acute optic neuritis, spontaneous visual recovery usually begins in the first 4 to 6 weeks, with continued improvement and good visual prognosis by 6 to 12 months. Ninety-four percent recover to 20/40 or better, and 3% of patients remain with 20/200 or worse visual outcome after 5 years, based on the Optic Neuritis Treatment Trial (ONTT) results. However, those with visual recovery still had residual deficits such as decreased contrast sensitivity. The clinical decision to manage and treat a patient with typical optic neuritis with steroids is often challenging. The ONTT was a multicentered, randomized, controlled clinical trial designed to evaluate the efficacy and safety of oral prednisone (1 mg/kg daily for 2 weeks) vs. intravenous methylprednisolone (250 mg 4 times daily for 3 days, followed by prednisone 1 mg/ kg daily for 11 days) compared with oral placebo for the treatment of acute optic neuritis. Primary outcome measures were contrast sensitivity and visual field, and secondary measures were vision and color. In summary, the ONTT revealed the IV steroid-treated patients recovered visual function faster within the first 4-6 weeks following onset of optic neuritis, but showed no statistical difference in final visual outcome from the IV steroid-treated patients and those receiving placebo. Oral steroids are contraindicated for acute optic neuritis because of a higher rate of recurrence of optic neuritis. Treatment varies among clinicians despite the ONTT. Some clinicians treat patients with 1 gm per day infused over 3 to 5 days in an outpatient infusion center. Some use oral prednisone thereafter, while others have abandoned it. The potential side effects and complications should be discussed with the patient prior to administration. Oral steroids alone are always contraindicated for acute optic neuritis because of an increased rate of recurrences of optic neuritis. But all patients with abnormal MRIs should be referred to the neurologist for further evaluation and management for MS. Institution of disease-modifying therapy should be discussed. OCT of the nerve fiber layer is a useful supplementary test to measure optic nerve structure in patients with optic neuritis. OCT can quantify the initial swelling and subsequent atrophy of the retinal nerve fiber layer as disc pallor develops at 6-8 weeks following the onset of an acute, isolated optic neuritis. Often, the optic atrophy can be subtle on funduscopic examination. The OCT provides a quantitative measure of the retinal nerve fiber layer thickness that can document the degree of optic atrophy. Section I: Vision Loss 2015 Subspecialty Day | Neuro-Ophthalmology Selected Readings C. Dry AMD 1.Basic and Clinical Science Course Section 5: Neuro-Ophthalmology, 2009-2010. San Francisco: AAO, 2009: 111-172. D. Macular edema 2. Cleary PA, Beck RW, Anderson MM Jr, Kenny DJ, Backlund JY, Gilbert PR. Design, methods, and conduct of the Optic Neuritis Treatment Trial. Control Clin Trials. 1993; 14(2):123-142. 1. Postoperative cystoid macular edema (CME) 2. Diabetic macular edema 29 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. Fisher JB, Jacobs FA, Markowitz CE, et al. Relation of visual function to retinal nerve fiber layer thickness in multiple sclerosis. Ophthalmology 2006; 113:324-332. 4. Systemic medications (thiazolidinediones, fingolimid, tamoxifen, taxanes, niacin, interferon) 5. Ocular medications (prostaglandin analogs, epinephrine, timolol) 5. Gea Y. Multiple sclerosis: the role of MR imaging. AJNR Am J Neuroradiol. 2006; 27:1165-1176. E. Infectious (toxoplasmosis, presumed ocular histoplasmosis, diffuse unilateral subacute neuroretinitis) 6. Jirawuthiworavong GV, Miller AM, Fajardo D. Demyelinating optic neuritis. 2015. EyeWiki website: eyewiki.org/demyelinating_optic_neuritis. F. Inflammatory (sarcoidosis, Vogt-Koyanagi-Harada syndrome, posterior scleritis, serpiginous chorioretinopathy, autoimmune retinopathy) G. Retinitis pigmentosa and allied disorders H. Toxicity (hydroxychloroquine, chloroquine, thioridazine, chlorpromazine, quinine) I. Macular dystrophy (cone-rod dystrophy, Best disease, Stargardt disease) J. Macular telangiectasia 7. Kappos L, Freedman MS, Polman CH, et al; BENEFIT Study Group. Long-term effect of early treatment with interferon beta-1b after a first clinical event suggestive of multiple sclerosis: 5-year active treatment extension of the Phase 3 BENEFIT trial. Lancet Neurol. 2009; 8(11):987-997. 8. McKinney AM, Lohman BD, SarikayaB, Benson M, Lee MS, Benson MT. Accuracy of routine fat-suppressed FLAIR and diffusionweighted images in detecting clinically evident acute optic neuritis. Acta Radiol. 2013; 54:455-461. 9. Optic Neuritis Study Group. The 5-year risk of MS after optic neuritis: experience of the Optic Neuritis Treatment Trial. Neurology 1997; 49:1404-1413. K. White dot syndromes (AZOOR) L. Nutritional vitamin A deficiency 10. Optic Neuritis Study Group. High- and low-risk profiles for the development of multiple sclerosis within 10 years after optic neuritis. Arch Ophthalmol. 2003; 121:944-949. 11. Optic Neuritis Study Group. Multiple sclerosis risk after optic neuritis: final Optic Neuritis Treatment Trial follow-up. Arch Neurol. 2008; 65(6):727-732. M. Paraneoplastic syndromes 1. Cancer-associated retinopathy (CAR) 2. Melanoma-associated retinopathy (MAR) N. Tumor-ocular melanoma O. Radiation-induced retinopathy II. Optic Nerve A.Glaucoma B. Compressive lesions affecting the optic nerve anterior to the chiasm (cerebral meningioma, aneurysm) Guy V Jirawuthiworavong MD C. Optic nerve meningioma / optic nerve glioma D. Toxic optic neuropathy (ethambutol, linezolid) Final Diagnosis E. Nutritional optic neuropathy (post-gastric bypassB12, folate, thiamine) F. Hereditary optic neuropathy-dominant optic atrophy (Kjer’s) “I am slowly losing vision in one of my eyes.” Acute zonal occult outer retinopathy (AZOOR) Teaching Points In summary, this patient presents with unilateral visual loss with a relative afferent pupillary defect, pericentral scotoma, and sectoral retinal pigmented epithelial atrophy corresponding to visual field, OCT, and fluorescein angiography findings, consistent with the diagnosis of AZOOR. Broad differential diagnosis of gradual, unilateral visual loss: I.Retina A. Vitreoretinal interface disorders (epiretinal membrane, vitreomacular traction, macular hole) B. Central serous chorioretinopathy The fundus findings of retinal pigmented epithelial atrophy narrows the differential diagnosis to retinal causes. OCT of the macula shows thinning of the outer retina, but there is no vitreomacular traction, intraretinal fluid, or subretinal fluid. The patient’s history of photopsias, nyctalopia, scotoma, and gradual progression is consistent with conditions such as retinitis pigmentosa, cone-rod dystrophy, white dot syndrome, autoimmune retinopathy, or a paraneoplastic syndrome. Blind spot enlargement can be the first visual field defect seen in retinitis pigmentosa. However, asymmetry of fundus findings and a relative afferent pupillary defect (RAPD) are exceptions to the rule in patients with retinitis pigmentosa, as well as in cone-rod dystrophy and 30 Section I: Vision Loss autoimmune retinopathy (AIR). Color vision is not spared in cone-rod dystrophy. CAR, MAR, and AIR patients have attenuated vasculature but otherwise have no other typical retinal findings. MAR patients usually present with a preceding diagnosis 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 eye shows peripapillary changes seen on fluorescein angiography. 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. AZOOR is an idiopathic inflammatory syndrome that affects young women more than men. AZOOR patients may complain of gradual loss of vision over time with constant photopsias. They often present with an enlarged blind spot that later progresses into a temporal / zonal visual field defect. This condition can affect one or both eyes and tends to be asymmetric in presentation. Central vision can be spared, and there is minimal RAPD at onset. Patients present acutely without any retinal changes on exam, and as a result, the diagnosis is often made many years later as the RPE changes are noted in follow-up. Patient’s family members can have an underlying autoimmune condition. AZOOR is diagnosed by history and retinal exam and can be confirmed by visual field testing, fluorescein angiogram, and 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 with the optic nerve. The newest imaging modality of fundus autofluorescence can show characteristic zones of hyperfluorescence at the leading edge of the AZOOR. It is postulated that AZOOR is either an autoimmune dysregulatory condition or a viral infectious disease entering the optic disc, but its etiology remains to be determined. Unlike AZOOR, retinitis pigmentosa (RP) can present at any age and tends to follow the rules of mendelian genetics, except in simplex RP. The common visual field defect is a ring scotoma but, as mentioned earlier, can uncommonly present with an enlarged blind spot on visual field testing. Fundus findings of bone spicules are sine qua non for RP, whereas AZOOR may or may not have any hyperpigmented spots. 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 macular 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 “My doctor says I might have glaucoma.” Jacinthe Rouleau MD Final Diagnosis Prior nonarteritic anterior ischemic optic neuropathy Teaching Points 1. Be aware that various optic neuropathies can mimic glaucomatous visual fields or cupping. 2. Clues that raise the suspicion of nonglaucomatous cupping are pallor of the rim, reduced central acuity or color vision loss out of proportion to disc cupping, atypical visual field defects, discordance between visual fields and cupping, marked relative afferent pupillary defect, and patient age less than 50 years old. 3. When optic atrophy is suspected to be from an old nonarteritic anterior ischemic optic neuropathy (NAION) but prior optic nerve edema cannot be documented, appropriate imaging of the orbits is recommended to eliminate a compressive or infiltrative lesion. Selected Readings 1. Greenfield DS, Siatkowski RM, Glaser JS, Schatz NJ, Parrish RK 2nd. The cupped disc: who needs neuroimaging? Ophthalmology 1998; 105:1866-1874. 2. Fraser CL, White AJ, Plant GT, Martin KR. Optic nerve cupping and the neuro-ophthalmologist. J Neuroophthalmol. 2013; 33:377389. 3. Golnik K. Nonglaucomatous optic atrophy. Neurol Clin. 2010; 28:631-640. 4. Atkins EJ, Bruce BB, Newman NJ, Biousse V. Treatment of nonarteritic anterior ischemic optic neuropathy. Surv Ophthalmol. 2010; 55:47-63. 5. Lee AG, Chau FY, Golnik KC, Kardon RH, Wall M. The diagnostic yield of the evaluation for isolated unexplained optic atrophy. Ophthalmology 2005; 112:757-759. Section I: Vision Loss 2015 Subspecialty Day | Neuro-Ophthalmology “I lose my vision and then it comes back.” 31 “I’m losing vision in both eyes.” John J Chen MD Jeffrey Bennett MD PhD Final Diagnosis Final Diagnosis Vasospastic amaurosis fugax causing transient monocular vision loss This patient had both normal-tension glaucoma and compressive optic neuropathy, with the former leading to a delay in the diagnosis of the compressive element. Teaching Points Teaching Points Retinal vasospasm is a rare cause of amaurosis fugax. During an episode, funduscopic findings include arterial and venous narrowing due to reduced arterial blood flow, “box-carring” of the blood column, and collapse of the retinal veins. Between events, the fundus exam is normal. Rarely, events may result in vascular retinopathy or optic neuropathy. As vasospastic amaurosis is rare, the diagnosis should be made only after excluding visual and life-threatening vascular conditions in susceptible individuals. Critical conditions that are important to consider in the patient with transient monocular vision loss include carotid stenosis, cardiac emboli (valvular disease and paradoxical emboli), hypercoagulable states (antiphospholipid antibody syndrome), and vasculitis. In many, but not all instances, fundus findings may provide important clues such as cholesterol, calcific, or platelet-fibrin emboli, or choroidal changes (Elschnig spots). Carotid Doppler ultrasound, erythrocyte sedimentation rate, C-reactive protein, and echocardiography should be performed in all patients with vascular risk factors who have transient monocular vision loss. MR angiography should be added if there is any concern for carotid dissection. Since vasospastic amaurosis has been associated with polyarteritis nodosa and eosinophilic vasculitis, additional autoimmune serologies (ANA and ANCA) should be considered in suspicious cases. Also, given the reported association between vasospastic amaurosis and cluster / migraine headaches, a careful headache history may be helpful in making a diagnosis when other causes have been excluded. Vasospastic amaurosis is exquisitely responsive to calcium channel blockade. Verapamil 240-360 mg daily is often sufficient to resolve the recurrent events. 1. Compressive optic neuropathy causes a painless, progressive decline in vision, often affecting central vision first. With compressive optic neuropathy, the optic nerves initially appear normal without edema unless the lesion is anterior or causes obstructive hydrocephalus. Gradual pallor of the optic nerve with thinning of the retinal nerve fiber layer and ganglion cell layer is expected if not treated. Because compressive optic neuropathy is generally reversible if found early, progressive painless vision loss is a sign of retrobulbar compression until proven otherwise. 2. Patients can have two pathologies. This patient had normal-tension glaucoma with advanced cupping, which delayed the diagnosis of compressive optic neuropathy. While Occam’s razor of diagnostic parsimony typically holds true in medicine, we have to keep in mind Hickam’s dictum: “Patients can have as many diseases as they damn well please.”1 3. Compressive lesions can cause cupping of the nerve in some instances.2,3 Therefore, neuroimaging is required to evaluate for nonglaucomatous optic atrophy in patients with cupping from presumed normal-tension glaucoma who have atypical features, such as an age younger than 50 years old, decreased central visual acuity, pallor of the residual neuroretinal rim, visual field defects respecting the vertical midline, color vision deficits, or symptoms of hypothalamic-pituitary dysfunction.4 4. A central or cecocentral scotoma on visual field testing is almost always pathologic. Thompson and colleagues studied the ability to volitionally create functional visual fields and a cecocentral scotoma was the hardest to create.5 Selected Readings References 1. Bernard GA, Bennett JL. Vasospastic amaurosis fugax. Arch Ophthalmol. 1999; 117(11):1568-1569. 1. Hilliard AA, Weinberger SE, Tierney LM Jr., Midthun DE, Saint S. Clinical problem-solving: Occam’s razor versus Saint’s Triad. N Engl J Med. 2004; 350(6):599-603. 2. Petzold A, Islam N, Plant GT. Video reconstruction of vasospastic transient monocular blindness. N Engl J Med. 2003; 348(16):16091610. 3. Hill DL, Daroff RB, Ducros A, Newman NJ, Biousse V. Most cases labeled as “retinal migraine” are not migraine [review]. J Neuroophthalmol. 2007; 27(1):3-8. 2. Bianchi-Marzoli S, Rizzo JF 3rd, Brancato R, Lessell S. Quantitative analysis of optic disc cupping in compressive optic neuropathy. Ophthalmology 1995; 102(3):436-440. 3. Kupersmith MJ, Krohn D. Cupping of the optic disc with compressive lesions of the anterior visual pathway. Ann Ophthalmol (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 “Can my child see?” 2015 Subspecialty Day | Neuro-Ophthalmology Final Diagnosis Teaching Point 2 Once the diagnosis of optic nerve hypoplasia is made, whether bilateral or unilateral, further testing including neuroimaging and an endocrinologic evaluation should be performed to assess for features that would support the diagnosis of septo-optic dysplasia. These include absent septum pellucidum, dysgenesis / agenesis of the corpus callosum, and pituitary abnormalities. In the setting of septo-optic dysplasia, endocrine dysfunction may occur in spite of a normal radiographic appearance of the pituitary. Most commonly, defects in growth hormone are identified; however, panhypopituitarism may occur. Visual impairment secondary to bilateral optic nerve hypoplasia in the setting of septo-optic dysplasia Selected Readings Teaching Points 1. Borchert M. Reappraisal of the optic nerve hypoplasia syndrome. J Neuroophthalmol. 2012; 32:58-67. Gena Heidary MD PhD The presentation will include fundus photos, MRI findings suggestive of septo-optic dysplasia, and endocrine workup. In addition, I will provide recent follow-up details including VA and treatment of strabismus to document the natural history of optic nerve hypoplasia. Teaching Point 1 In an infant with subnormal vision for age, a framework for approaching the exam is to consider several general categories: a structural basis for visual impairment (eg, optic nerve hypoplasia, congenital cataracts), an inherited retinal dystrophy / degenerative process, cortical visual impairment, or delayed visual maturation. In this case, the clinical findings on the examination revealed abnormalities of the optic nerves, providing the etiology for the poor visual behavior. Because of the bilateral involvement, the baby presented with nystagmus; in contrast, children who harbor unilateral optic nerve hypoplasia will commonly present with a sensory strabismus. 2. Mohney BG, Young RC, Diehl N. Incidence and associated endocrine and neurologic abnormalities of optic nerve hypoplasia. JAMA Ophthalmol. 2013; 131:898-902. 3. Ahmad T, Borchert M, Geffner M. Optic nerve hypoplasia and hypopituitarism. Pediatr Endocrinol Rev. 2008; 5:772-777. 4. Ahmad T, Garcia-Filion P, Borchert M, Kaufman F, Burkett L, Geffner M. Endocrinological and auxological abnormalities in young children with optic nerve hypoplasia: a prospective study. J Pediatr. 2006; 148:78-84. 5. Garcia-Filion P, Fink C, Geffner ME, Borchert M. Optic nerve hypoplasia in North America: a re-appraisal of perinatal risk factors. 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 chiasm, any enlargement of the gland can lead to a chiasmal syndrome. As in any situation, a slowly growing mass will produce fewer symptoms than a rapidly expanding one. Depending on the patient’s specific anatomy and the anatomy of the tumor, however, patients may have a myriad of other effects involving the optic nerves, upper cranial nerves, and optic tracts. In pituitary apoplexy, the cells of the tumor infarct and/or bleed and very quickly put pressure upward on the diaphragma and laterally toward the cavernous sinuses. This is thought to be due to intrinsic marginal perfusion combined with high metabolic demands. It can cause the classic “thunderclap” headache or a more insidious onset of diplopia, ptosis, decreased vision, and light sensitivity evolving over hours to days. Headache is present > 95% of the time, and aberration of extraocular movements occurs in up to 75% of patients. Decrease in visual fields and, slightly less commonly, visual acuities are found in roughly half of patients. The incidence of apoplexy in pituitary tumors is 2%-12% (most commonly in nonfunctioning adenomas). It is the initial presentation of the tumor in about 80% of patients. There are several known associations with apoplexy, including cardiac surgery, insulin infusion, transient increased intracranial pressure, initiation of anticoagulation, and hypo- or hyperperfusion states. Surgical decompression of the optic apparatus, preferably from a ventral approach (trans-sphenoidal or expanded endonasal), results in improvement of visual deficits in more than 75% of patients whose symptoms have been present for less than a week. If the main ophthalmic sequela is ophthalmoplegia, most patients improve even with nonsurgical management. Surgical treatment of strabismus should be delayed by 6-12 months to ensure that natural recovery is complete. There are several different causes of painful Horner syndrome. Our patient’s most pertinent finding was a Horner syndrome. When working up Horner syndrome, particularly when painful, we recall that the sympathetic pathway to the eye consists of three “orders.” Wallenberg syndrome (lateral medullary syndrome) due to vertebral dissection can cause a painful first-order Horner syndrome but would be expected to have other features (eg, acute vestibular syndrome or crossed sensory loss). A painful Horner syndrome will usually be postganglionic (third order). The postganglionic sympathetic pathway traverses the carotid artery, skull base, cavernous sinus, and orbital apex. Painful postganglionic, nonisolated Horner syndrome etiologies include Tolosa-Hunt syndrome (orbital pseudotumor), skull-based nasopharyngeal carcinoma or inflammatory lesions, or orbital apex syndrome. These syndromes’ other clinical features will be specific to their location. An isolated, painful Horner syndrome mainly either involves the region of the superior cervical ganglion and internal carotid artery or presents without imaging abnormalities (as in the primary headache disorders). Considering this, the differential diagnosis for isolated painful Horner syndrome includes: Selected Readings 1. Oldfield EH, Merrill MJ. Apoplexy of pituitary adenomas: the perfect storm. J Neurosurg. 2015; 122(6):1444-1449. 2. Fraser CL, Biousse V, Newman NJ. Visual outcomes after treatment of pituitary adenomas. Neurosurg Clin N Am. 2012; 23(4):607619. 3. Briet C, Salenave S, Chanson P. Pituitary apoplexy. Endocrinol Metab Clin North Am. 2015; 44(1):199-209. • The trigeminal autonomic cephalgias (TACs) – Hemicrania continua – Paroxysma hemicrania – SUNA/SUNCT (short-lasting unilateral neuralgiform headaches with autonomic symptoms / short-lasting unilateral neuralgiform headaches with conjunctival injection and tearing) – Cluster headache • Internal carotid artery dissection • Raeder syndrome The trigeminal autonomic cephalgias are primary headache disorders. Raeder syndrome is also called oculopupillary sympathetic paralysis and is caused by lesion in the middle cranial fossa. A carotid dissection may be otherwise nonfocal. Distinguishing between these causes of an isolated painful Horner syndrome relies on both clinical and paraclinical investigation, which are described next. Cluster headache has certain features, which distinguish it from other similar syndromes. Perhaps the first description of cluster headache was by the British 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 across the left temple and forehead, and lasted for three-quarters of an hour, like an ‘electric battery,’ while his face became flushed and he felt faint. The neuralgia recurred thrice daily, at about eight-hour intervals, for six weeks, and then disappeared entirely for two years. Ever since his first attack he had left cervical sympathetic paralysis, there being slight ptosis, with a small pupil.”1 The International Classification of Headache Disorders2 defines cluster headaches as having “a sense of restlessness or agitation,” as well as conjunctival injection / lacrimation, nasal congestion / rhinorrhea, eyelid edema, forehead and facial flushing and sweating, ear fullness, or Horner syndrome. Headaches are severe, unilateral, orbital or supraorbital / temporal, and occur between 8/day to every other day and last 15-180 minutes each. The timing of the pain distinguishes it from the other trigeminal autonomic cephalgias. SUNCT/SUNA neuralgia lasts only seconds. Paroxysma hemicrania usually lasts 10-20 minutes, and hemicrania continua may last for days or more.3 During the typical 6-12 week cluster period, the headaches occur with clockwork regularity. Once a cluster period has completed, it may recur over a variable amount of time. On the other hand, the Horner syndrome may not resolve after the cluster, and in fact may never resolve in some cases. Response to treatments also somewhat distinguishes cluster headache from other headache syndromes. Both alcohol and smoking can be headache triggers. Abortive treatments include inhaled high-flow oxygen for 10-15 minutes, which can completely relieve pain. Triptans (eg, sumatriptan, zolmitriptan) provide acute pain relief during a cluster attack. Steroids (oral prednisone for 10-12 days) provide a bridge to prophylaxis, which often consists of verapamil, ~240 mg daily in divided doses. A painful Horner syndrome is a carotid dissection until proven otherwise. Although this patient ended up having cluster headaches, one clinical pearl to remember is that in the correct clinical context, a painful Horner syndrome should be considered a carotid dissection until proven otherwise. There may be no other neurologic signs, and in these cases the isolated presentation especially mimics a cluster headache. Up to 20% of spontaneous carotid dissections have a Horner syndrome,4 and 91% of carotid artery dissections that have a Horner syndrome are painful. Diagnosis is especially important because without treatment to prevent thromboembolism, the risk of stroke nears 20%.5 References 1. Harris W. Neuritis and Neuralgia. London: Humphrey Milford, Oxford University Press; 1926. 2. Headache Classification Committee of the International Headache Society. The International Classification of Headache Disorders, 2nd ed. Cephalalgia 2004; 24:1-160. 3. May A. Diagnosis and clinical features of trigemino-autonomic headaches. Headache 2013; 53:1470-1478. 4. Glaser JS. Neuro-ophthalmology. Philadelphia: Lippincott Williams & Wilkins, 1999. 5. Nautiyal A, Singh S, DiSalle M, O’Sullivan J. Painful Horner syndrome as a harbinger of silent carotid dissection. PLoS Med. 2005; 2(1):e19. 2015 Subspecialty Day | Neuro-Ophthalmology “My eye just aches all the time.” Rod Foroozan MD Final Diagnosis Greater occipital neuralgia Teaching Points 1. Highlights of the International Headache Society diagnostic criteria for greater occipital neuralgia include pain that is recurrent, severe, and shooting or stabbing in quality. Other criteria include dysesthesia or tenderness of the scalp.1 Symptoms from greater occipital neuralgia overlap other headache syndromes. The pain is thought to be caused by irritation of the greater occipital nerve with multiple potential sites from surrounding tissue.2,3 The distinction from other headache syndromes can be difficult but is aided by criteria outlined by the International Headache Society, 3rd edition. The anatomy of the greater occipital nerve and its relationship to the surrounding soft tissue is variable, but the nerve commonly originates from the medial branch of the dorsal ramus of C2. The greater occipital nerve then ascends between the inferior oblique capitis muscle and semispinalis capitis and pierces the semispinalis muscle. It then runs rostrolaterally and deep to the trapezius muscle and pierces the aponeurosis of the trapezius slightly inferior to the superior nuchal ridge, where it becomes subcutaneous and lies medial to the occipital artery. Branches then supply cutaneous sensation to the posterior scalp from the external occipital protuberance to the vertex. Please see Figures 1 and 2 from reference #3 listed below for the pertinent anatomy and potential sites of compression of the greater occipital nerve.3 2. The eye examination should not reveal other causes for pain, and other primary (such as migraine) and secondary (giant cell arteritis, cervical spine disease) headache syndromes should be excluded by history, physical examination, and ancillary testing. Irritation of the greater, lesser, and third occipital nerves can all lead to symptoms categorized as occipital neuralgia. Pain may occur in the frontal area or the orbit through trigeminocervical interneuronal connections in the trigeminal spinal nuclei. When greater occipital neuralgia involves the orbit, the eye may be the presumed site of pathology; however, the eye examination does not reveal any abnormalities that would cause pain.4 Degenerative conditions involving the cervical spine can cause pain in a similar pattern to occipital neuralgia, and in these patients, imaging of the skull base and cervical spine should reveal an abnormality. 3. Relief of pain along the course of the greater occipital nerve with an injection of local anesthetic helps suggest the diagnosis but is not pathognomonic, as other headache syndromes such as migraine may be relieved by these injections. The pain from occipital neuralgia may respond to oral agents such as gabapentin, carbamazepine, and tricyclic antidepressants. However, injection of local anesthetic (typically lidocaine or bupivacaine) has been thought to be more likely to relieve the pain from occipital neuralgia, but may also relieve pain from 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 Section II: Eye Pain and Headache 2015 Subspecialty Day | Neuro-Ophthalmology 2 cm inferiorly. Palpation for pulsation and aspiration prior to injection helps avoid involvement of the occipital artery. Some authors have suggested mixing corticosteroids with local anesthetic, although there is no proof that this adds additional benefit. Injection of botulinum toxin in the same anatomic area has also been reported to limit the pain from greater occipital neuralgia in a small group of patients. Some patients may not respond to oral agents or local anesthetic injections. Neuromodulation using high-voltage radio frequency has been reported to improve pain, and occipital nerve stimulation using an implanted stimulator has also been noted to be effective for some refractory patients. Surgical decompression has been noted to be curative in some patients. The International Headache Society diagnostic criteria for occipital neuralgia1 A. Unilateral or bilateral pain fulfilling criteria B-E B. Pain is located in the distribution of the greater, lesser and/or third occipital nerves. C. Pain has two of the following three characteristics: 1. Recurring in paroxysmal attacks lasting from a few seconds to minutes 2. Severe intensity 3. Shooting, stabbing, or sharp in quality D. Pain is associated with both of the following: 1. Dysesthesia and/or allodynia apparent during innocuous stimulation of the scalp and/or hair 2. Either or both of the following: a. Tenderness over the affected nerve branches b. Trigger points at the emergence of the greater occipital nerve or in the area of distribution of C2 E. Pain is eased temporarily by local anesthetic block of the affected nerve. F. Not better accounted for by another ICHD-3 diagnosis 35 “The light!! It hurts my eyes!!” Bradley J Katz MD Discussion Photophobia, an abnormal intolerance to light, is associated with a number of ophthalmic and neurologic conditions. However, in the presence of a normal neuro-ophthalmic examination, the most common conditions associated with photophobia are migraine, blepharospasm, and traumatic brain injury. Recent evidence indicates that the intrinsically photosensitive retinal ganglion cells play a key role in the pathophysiology of photophobia. Although pharmacologic manipulation of intrinsically photosensitive retinal ganglion cells may be possible in the future, current therapies are directed at optical modulation of these cells. Teaching Points 1. Most patients with light sensitivity do not have an ocular problem (eg, iritis). 2. Most patients with light sensitivity have migraine, although it may be undiagnosed or misdiagnosed. 3. The purpose of the ophthalmic exam is to rule out other light sensitive conditions, such as dry eye and blepharospasm. 4. Management includes optical treatments for indoor and outdoor light sensitivity and referral to a headache specialist or neurologist. Selected Readings 1. Blackburn MA, Lamb R, Digre KB, et al. FL-41 tint improves blink frequency, light sensitivity, and functional limitations in patients with benign essential blepharospasm. Ophthalmology 2009; 116:997-1001. 2. Digre KB, Brennan KC. Shedding light on photophobia. J Neuroophthalmol. 2012; 32:68-81. 3. Güler AD, Ecker JL, Lall GS, et al. Melanopsin cells are the principal conduits for rod-cone input to non-image-forming vision. Nature 2008; 453:102-105. References 4. Hattar S, Liao HW, Takao M, Berson DM, Yau KW. Melanopsincontaining retinal ganglion cells: architecture, projections, and intrinsic photosensitivity. Science 2002; 295:1065-1070. 1. The International Classification of Headache Disorders, 3rd ed. (beta version). Cephalalgia 2013; 33:629-808. 5. Kawasaki A, Kardon RH. Intrinsically photosensitive retinal ganglion cells. J Neuroophthalmol. 2007; 27:195-204. 2. Dougherty C. Occipital neuralgia. Curr Pain Headache Rep. 2014; 18:411. 6. Noseda R, Kainz V, Jakubowski M, et al. A neural mechanism for exacerbation of headache by light. Nat Neurosci. 2010; 13:239245. 3. Cesmebasi A, Muhleman MA, Hulsberg P, et al. Occipital neuralgia: anatomic considerations. Clin Anat. 2015; 28:101-108. 4. Lee AG, Brazis PW. The evaluation of eye pain with a normal ocular exam. Semin Ophthalmol. 2003; 18:190-199. 7. Noseda R, Burstein R. Advances in understanding the mechanisms of migraine-type photophobia. Curr Opin Neurol. 2011; 24:197202. 36 Section II: Eye Pain and Headache “It hurts when I talk, and this cough won’t go away.” Gabrielle R. Bonhomme MD Final Diagnosis Temporal arteritis presenting with persistent cough, trismus, and transient diplopia. Discussion Temporal arteritis (GCA) is a medium to large vessel vasculitis that commonly presents with visual symptoms due to anterior ischemic optic neuropathy (AION) (94%) and classic constitutional symptoms of new-onset headache, jaw claudication, scalp tenderness, and polymyalgia rheumatica (PMR). The incidence of GCA increases in patients older than 50 years of age, ranging from 18 to 27 cases per 100,000 in people over 50 years of age. Genetic associations with HLA-DR4 and HLA-DRB1 exist.1 The American College of Rheumatology (ACR) requires 3 of the following 5 criteria for diagnosis: 1. Age of 50 year or older 2. New headache 3. Temporal artery abnormality (tenderness to palpation or decreased pulsation) 4. ESR > 50 mm/h 5. Abnormal findings on temporal artery biopsy (evidence of vasculitis)1 However, patients may present without classic systemic symptoms or with a variety of atypical, nonspecific constitutional symptoms, particularly early in the course of the disease. Further, occult GCA may present with ocular involvement in the absence of systemic signs or symptomatology in 21% of patients.2 Given these atypical cases, a recent study estimates that the ACR criteria used in isolation may miss up to 25% of cases of GCA.3 While studies have quoted the specificity of ESR and CRP in combination to be 97%,4 GCA may occur in the absence of abnormally elevated inflammatory markers. Therefore, it behooves the ophthalmologist both to identify expected ocular signs of GCA and to recognize atypical systemic symptoms indicative of evaluation for temporal arteritis to properly direct patient management. In addition to large vessel involvement such as aortitis and aortic aneurysm, otolaryngeal and respiratory disorders such as intractable, nonproductive cough, trismus, and tongue infarction resulting from ischemia of affected tissues 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 of patients with biopsy-proven GCA, often in association with other systemic symptoms or elevated CRP, as seen in our patient. Early recognition of dry cough in an elderly patient as a potential 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 of GCA, and resultant vision loss.7 Teaching Points 1. Temporal arteritis (GCA) should be considered in the differential diagnosis when an elderly patient presents with new-onset headache. 2. Recognition of less common, non-ocular signs of ischemia, such as cough, trismus, and jaw claudication, is crucial to the early diagnosis and therefore timely treatment of GCA. 3. Occult GCA should be suspected in patients over the age of 50 years with AION and the above symptoms, even in the absence of abnormal inflammatory markers such as ESR and CRP. References 1. Hunder GG, Bloch DA, Michel BA, et al. The American College of Rheumatology 1990 criteria for the classification of giant cell arteritis. Arthritis Rheum. 1990; 33(8):1122-1128. 2. Hayreh SS, Podhajsky PA, Zimmerman B. Occult giant cell arteritis: ocular manifestations. Am J Ophthalmol. 1998; 125(6):893. 3. Murchison AP, Gilbert ME, Bikyk JR, et al. Validity of the American College of Rheumatology criteria for the diagnosis of giant cell arteritis. Am J Ophthalmol. 2012; 154:617-619. 4. Hayreh SS, Podhajsky PA, Raman R, et al. Giant cell arteritis: validity and reliability of various diagnostic criteria. Am J Ophthalmol. 1997; 123(3):285-296. 5. Parikh M, Miller NR, Lee AG, et al. Prevalence of a normal C-reactive protein with an elevated erythrocyte sedimentation rate in biopsy-proven giant cell arteritis. Ophthalmology 2006; 113(10):1842-1845. 6. Imran TF, Helfgott S. Respiratory and otolaryngologic manifestations of giant cell arteritis. Clin Exp Rheumatol. 2015; 89(2):164170. 7. Zenone T, Puget M. Dry cough is a frequent manifestation of giant cell arteritis. Rheumatol Int. 2013; 33:2165-2168. 8. El-Dairi MA, Chang L, Bhatti T, et al. Diagnostic algorithm for patients with suspected giant cell arteritis. J Neuro-Ophthalmol. Epub ahead of print 2015 Mar 23. 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 way.” Paul H Phillips MD Final Diagnosis Right CN III palsy, CN VI palsy, and Horner syndrome from a right cavernous sinus meningioma Cranial nerve VI innervates the lateral rectus muscle, and therefore a CN VI palsy is characterized by an abduction deficit that increases with gaze toward the affected eye and at distance.1 Injury may occur at multiple locations, including the nucleus, fascicle, subarachnoid space, cavernous sinus, and orbit. Multiple etiologies may cause CN VI dysfunction, including ischemia, compression, inflammation (multiple sclerosis, sarcoidosis), infection, and trauma. An increase or decrease in intracranial pressure may shift the brainstem and stretch CN VI, resulting in a unilateral or bilateral CN VI palsy. Thus, it is important to evaluate the disc for papilledema in patients that present with CN VI palsy. Microvascular ischemia to the subarachnoid segment of the nerve is a common cause of an isolated sixth-nerve palsy. The following characteristics support an ischemic etiology:2 • Age greater than 50 • Arteriosclerotic risk factors such as hypertension, diabetes mellitus, hypercholesterolemia, tobacco use • No history of cancer • The abduction deficit remains isolated during follow-up examination. • The abduction deficit stabilizes after 1-2 weeks and improves in 3-4 months. If patients fulfill these criteria, many investigators will presume a microvascular etiology and not obtain neuroimaging at onset. Associated risk factors such as diabetes and hypertension should be evaluated, and the patient should be followed to confirm improvement of the abduction deficit within 3-4 months. Progressive or unresolved palsies or additional neurological deficits mandate further neuroimaging. Murchison et al2 showed that following this algorithm is cost-effective and unlikely to miss an alternative, treatable etiology. However, Chou et al3 showed that 4 of 19 patients (21%) with CN VI palsy that fulfilled these criteria had nonischemic etiologies, including neoplasm, brainstem infarct, multiple sclerosis, and pituitary apoplexy, and recommend neuroimaging at presentation of all patients with CN VI palsy. Additional neurological deficits allow more refined localization and mandate neuroimaging. Further diagnostic testing should be considered, including lumbar puncture, chest imaging, and hematologic studies for etiologies such as syphilis, sarcoidosis, and collagen vascular disease. A brainstem lesion affecting the sixth cranial nerve nucleus will cause a gaze palsy (neither eye can rotate horizontally to the side of the CN VI nuclear lesion), often accompanied by CN VII palsy as cranial nerve VII fibers curve around the sixth nerve nucleus. Brainstem lesions that affect the fascicle of the sixth nerve may also damage the seventh nerve fascicle, tractus solitarius, and the descending tract of the trigeminal nerve, causing an ipsilateral abduction deficit, facial paresis, loss of taste over the anterior 2/3 of the tongue, and facial hypoesthesia (Foville syndrome). Lesions located in the ventral pons may affect the sixth cranial nerve, seventh cranial nerve, and the corticospinal tract, resulting in an ipsilateral abduction deficit, facial weakness, and contralateral hemiplegia (Millard-Gubler syndrome). Lesions of the cerebellopontine angle may affect CN V (decreased facial sensation), CN VI (abduction deficit), CN VII (facial weakness), and CN VIII (decreased hearing and vestibular dysfunction). Inflammation in the petrous bone may cause an ipsilateral CN VI palsy and facial pain (Gradenigo syndrome). An abduction deficit accompanied by proptosis suggests an orbital process affecting CN VI or the extraocular muscles (thyroid orbitopathy, orbital pseudotumor). The cavernous sinus contains cranial nerves III, IV, V1, V2, and VI, as well as the third-order, postganglionic ocular sympathetic fibers. Any combination of ipsilateral dysfunction of these cranial nerves suggests cavernous sinus involvement. The third-order postganglionic sympathetic fibers ascend with 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 the ophthalmic branch of the trigeminal nerve and enter the orbit through the superior orbital fissure. Therefore, the combination of a CN VI palsy and an ipsilateral postganglionic Horner syndrome localizes the pathology to the posterior cavernous sinus. Our patient presented with an isolated CN VI palsy that was consistent with an ischemic etiology. However, he subsequently developed an ipsilateral Horner syndrome as well as CN III paresis, suggesting cavernous sinus pathology. Neuroimaging confirmed a cavernous sinus lesion consistent with a meningioma. Teaching Points 1. Ischemic cranial nerve palsies do not typically affect multiple cranial nerves simultaneously. 2. Ischemic cranial nerve palsies should improve over 3-4 months. 3. Unilateral dysfunction of multiple cranial nerves (III, IV, V1, V2, and VI) suggests cavernous sinus localization. 4. The sympathetic fibers travel with CN VI in the posterior cavernous sinus. Therefore, the combination of CN VI palsy and Horner syndrome suggests cavernous sinus localization. 5. Controversy exists over whether to image an isolated CN VI palsy in the vasculopathic older patient after the initial visit, or to monitor closely. 38 Section III: Double Vision and Nystagmus References 1. “The patient with diplopia.” In: Neuro-Ophthalmology: Basic and Clinical Science Course. San Francisco: American Academy of Ophthalmolgy 2014-2015: section 5, chapter 8, 212-221. 2. Murchison AP, Gilbert ME, Savino PJ. Neuroimaging and acute ocular motor mononeuropathies: a prospective study. Arch Ophthalmol. 2011; 129(3):301-305. 3. Chou KL, Galetta SL, Liu GT, et al. Acute ocular motor mononeuropathies: prospective study of the roles of neuroimaging and clinical 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. Ophthalmology 1986; 93:913-916. 5. Tsuda H, Ishikawa H, Kishiro M, Koga N, Kashima Y. Abducens nerve palsy and postganglionic Horner syndrome with or without severe headache. Intern Med. 2006; 45(14):851-855. “I see two golf club heads when I putt.” Courtney E Francis MD Final Diagnosis Thyroid eye disease with left inferior rectus restriction Teaching Points On further review, the patient had a remote history of Graves disease, treated with methimazole and currently in remission. He was followed over time to ensure stability of his deviation for at least 6 months. He underwent left inferior rectus recession of 6 mm, with resolution of his symptoms. Small deviations may be managed conservatively with prism glasses. As alignment may change following surgery, orbital decompressions should always be performed first if clinically indicated and lid surgery should be reserved until after strabismus surgery. Care should be taken to avoid overcorrection in cases of inferior rectus recession, which could lead to diplopia in downgaze. Additionally, some patients with restrictive strabismus from thyroid eye disease can have late overcorrection after surgery. Selected Readings 1. Harrad R. Management of strabismus in thyroid eye disease. Eye 2015; 29:234-237. 2. Peragallo JH, Velez FG, Demer JL, Pineles SL. Postoperative drift in patients with thyroid ophthalmopathy undergoing unilateral inferior rectus muscle recession. Strabismus 2013; 21(1):23-28. 3. Volpe NJ, Mirza-George N, Binenbaum G. Surgical management of vertical ocular misalignment in thyroid eye disease using an adjustable suture technique. J AAPOS. 2012; 16(6):518-522. 4. Bothun ED, Scheurer RA, Harrison AR, Lee MS. Update on thyroid eye disease and management. Clin Ophthalmol. 2009; 3:543-551. 5. Chen VM, Dagi LR. Ocular misalignment in Graves disease may mimic that of superior oblique palsy. J Neuroophthalmol. 2008; 28(4):302-304. 2015 Subspecialty Day | Neuro-Ophthalmology “Things are blurry and jumpy when I read.” Janet C Rucker MD Final Diagnosis Paraneoplastic cerebellar degeneration with downbeat nystagmus and gait ataxia and positive paraneoplastic antibodies due to recurrent ovarian cancer Teaching Points Teaching Point 1: Nystagmus Nystagmus is a spontaneous, repetitive movement of the eyes that is initiated by slow eye drifts away from desired eye position. It may be jerk (slow drifts followed by corrective fast movements 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 beating,” “up beating,” etc.). Both jerk and pendular nystagmus may have horizontal, vertical, and/or torsional components. Oscillopsia, a subjective sensation of visual motion, is often experienced 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 gaze with motion in the vertical direction. The first two are jerk 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 movements upwards. It is, by definition, present in primary gaze and is typically more prominent in upgaze. UBN is much less common than DBN and APN and is most typically seen in multiple sclerosis and Wernicke encephalopathy. DBN consists of slow drifts of the eyes upward with corrective fast movements downward. It is, by definition, present in primary gaze, but it may be of such low amplitude that it is invisible to the naked eye. It is much more prominent in lateral, downward gaze (and is thus sometimes called “side-pocket nystagmus”). It is often absent or converted to upbeat nystagmus in upgaze. A chin-down resting head position may be adopted by the patient to minimize oscillopsia. Strategies to optimize visualization of DBN in primary gaze include viewing the eye at the slit 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 it is an isolated finding. Other common causes include Chiari I malformation, other cervicomedullary junction pathology, and substance toxicities (eg, anti-convulsants, lithium, alcohol). DBN is also commonly seen in association with cerebellar disease from structural abnormalities on MRI (eg, stroke, tumor), genetic spinocerebellar degenerations, or with neurologically active antibodies in the serum (eg, anti-GAD antibodies, paraneoplastic antibodies). The best-studied treatments for DBN are the potassium channel blockers 4-aminopyridine (4-AP) and 3,4-diaminopyridine (3,4-DAP), in addition to chlorzoxazone and gabapentin. APN consists of slow pendular oscillations of the eyes without fast corrective movements. It is commonly seen in two scenarios: multiple sclerosis and oculopalatal tremor (OPT). In OPT, it 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 increased T2 signal in and hypertrophy of the inferior olives in the medulla. APN in MS often has a horizontal or elliptical trajectory. In OPT, it is often vertical. The two most effective treatments for APN are gabapentin and memantine. Teaching Point 2: Paraneoplastic syndromes Paraneoplastic syndromes cause cancer-related, immunemediated, acute to subacute decline in nervous system function remote from a cancer site. They are most commonly associated with small-cell cancers such as lung cancer but are also often seen with ovarian and breast carcinoma and testicular germ cell tumors. Typical paraneoplastic syndromes that involve vision include optic neuropathy, retinopathy, cerebellar degeneration with downbeat nystagmus, and opsoclonus. Paraneoplastic antibodies are commonly present in serum. It is very important to be aware that the cancer is often occult and undiagnosed at time of onset of the visual or neurological symptoms, and intensive, exhaustive search for an underlying malignancy is critical. If no malignancy is identified and a paraneoplastic syndrome is strongly suspect, periodic surveillance for malignancy should be performed annually for at least 5 years. Section III: Double Vision and Nystagmus 39 signs or symptoms, or history of onset after trauma are important. In this setting, neurologic workup with imaging and/or lumbar puncture may be helpful. Selected Readings 1. Liu GT, Volpe NJ, Galetta SL. Eye movement disorders: third, fourth, and sixth nerve palsies and other causes of diplopia and ocular misalignment. In: Neuro-ophthalmology: Diagnosis and Management, 2nd ed. New York: Saunders Elsevier; 2010:491-550. 2. Kline LB, Foroozan R. Supranuclear and internuclear gaze pathways. In: Neuro-Ophthalmology Review Manual, 7th ed. Thorofare, NJ: SLACK Inc.; 2013:45-72. 3. Jacobson DJ. Divergence insufficiency revisited: natural history of idiopathic cases and neurologic associations. Arch Ophthalmol. 2000; 118:1237-1241. 4. Chaudhuri Z, Demer JL. Sagging eye syndrome: connective tissue involution as a cause of horizontal and vertical strabismus in older patients. JAMA Ophthalmol. 2013; 131(5):619-625. 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. 2. Thurtell MJ, Leigh RJ. Nystagmus and saccadic intrusions. Handb Clin Neurol. 2011; 102:333-378. 3. Rucker JC. An update on acquired nystagmus. Semin Ophthalmol. 2008; 23:91-97. 4. Ko MW, Dalmau J, Galetta SL. Neuro-ophthalmologic manifestations of paraneoplastic syndromes. J Neuroophthalmol. 2008; 28:58-68. “Words run together on the TV.” Kimberly M Winges MD Final Diagnosis Divergence insufficiency, secondary to spinocerebellar ataxia Teaching Points 1. Divergence insufficiency (DI) is defined as a comitant esophoria or esotropia worse at distance than near (or absent at near), with full ductions and no evidence of cranial nerve palsy. 2. DI can be secondary to neurologic causes, or it can be primary (idiopathic). A poorly defined divergence center in the caudal pons is hypothesized to be responsible for neurologic divergence paralysis. More recently, involutional changes within the orbital connective tissue and extraocular muscles have been recognized as non-neurologic causes of distance esotropia in older individuals. Most patients with DI in isolation do not develop future neurologic disease. 3. The main differential diagnosis of DI is bilateral CN VI palsy, and careful attention to signs of increased intracranial pressure, other cranial nerve involvement, neurologic “I see double when I get tired.” Marc J Dinkin MD Final Diagnosis Myasthenia gravis 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. 3. Other strabismus patterns that suggest a congenital origin 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 limitation of abduction of an eye (suggestive of a Duane syndrome). 4. Specific exam features that help confirm a congenital origin are: • High fusional amplitude: When increasing prism is added in the vertical plane, for example, above and beyond what is needed to remove the phoria, the patient with congenital strabismus will often continue to be able to fuse the two images, without diplopia, over a large number of additional prism diopters. In contrast, the myasthenic patient, who has not had a lifetime to cortically adapt to the strabismus, will typically not have a high fusional amplitude. • The finding of a compensatory head turn or tilt on old photos • In the case of a limitation of abduction, the presence of retraction on adduction is highly suggestive of Duane’s syndrome.1 • In the case of limited elevation on adduction, a positive forced duction test suggests a restriction of the superior oblique tendon consistent with Brown syndrome. 40 Section III: Double Vision and Nystagmus 5. Fatigable ptosis on sustained upgaze suggests ocular myasthenia but may also be present in up to 38% of patients who do not have the disease.2 6. The onset of a new fatigable ptosis over a background of fatigable diplopia is highly suggestive of myasthenia gravis, making decompensation of a congenital strabismus as the cause of the diplopia much less likely. However, some patients presenting with a decompensation of a congenital strabismus may also have ptosis from other causes, most often mechanical. And in fact, such a lid may also be more difficult to keep up when the patient is tired. Thus, the combination of ptosis and fatigable diplopia should not be looked at as pathognomonic for myasthenia. 7. Lack of systemic fatigable weakness is consistent with a diagnosis of ocular myasthenia, although in a recent study, 20.9% of patients will convert to generalized myasthenia over the next two years.3 8. The presence of enhanced ptosis (curtaining) is not specific to ocular myasthenia, as it reveals a weakness of the apparently uninvolved levator palpebrae muscle which is brought out by passive lifting of the ptotic lid,4 although it has been described in other conditions as well.5 This is an example of Herring’s Law: that the force put into one extraocular muscle is equal in both eyes. Cogan lid twitch is another finding classic for ocular myasthenia6 but is not ubiquitously observed.7 9. The Tensilon test has a high specificity for myasthenia but may cause syncope or, rarely, cardiac arrhythmias.8 10. The rest test is a sensitive and specific assessment for ocular myasthenia but requires rigorous documentation before and after a 20-minute session of eye closure.9 11. A decrement on repetitive nerve stimulation (RNS) testing is highly specific for myasthenia,10 but the test has a sensitivity as low as 24%2 so that a lack of decrement does not rule out myasthenia. Single fiber EMG may reveal increased jitter in cases of OMG, and has a higher sensitivity (90%-95%) than RNS,11 but it requires arduous and time-consuming testing and is only performed by select experts. 12. Acetylcholine receptor antibodies may be elevated in pure ocular myasthenia, but sensitivity is low, ranging from 14.1%12 to 50%.13 13. Some patients with ocular myasthenia harbor a thoracic thymoma, and in rare cases the tumor may be malignant,14 or even more rarely, as in this case, be composed of amyloid.15,16 14. Other entities that may mimic ocular myasthenia because of a diurnal variability include Miller Fisher syndrome17 and silent sinus syndrome.18 The latter is associated with hypoglobus, or inferior positioning of the globe, due to an inferior bowing of the orbital flow into a low pressure maxillary sinus, thus producing a vertical diplopia.19 Such “sinking” may worsen later in the day due to the effects of gravity, thus mimicking the fatigability of myasthenia. 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 3. Nagia L, Lemos J, Abusamra K, Cornblath WT, Eggenberger ER. Prognosis of ocular myasthenia gravis: retrospective multicenter analysis. Ophthalmology. Epub ahead of print 2015 Apr 16. doi: 10.1016/j.ophtha.2015.03.010. 4. Gorelick PB, Rosenberg M, Pagano RJ. Enhanced ptosis in myasthenia gravis. Arch Neurol. 1981; 38(8):531. 5. Ishikawa H, Wakakura M, Ishikawa S. Enhanced ptosis in Fisher’s syndrome after Epstein-Barr virus infection. J Clin Neuroophthalmol. 1990; 10(3):197-200. 6. Cogan DG. Myasthenia gravis: a review of the disease and a description of lid twitch as a characteristic sign. Arch Ophthalmol. 1965; 74:217-221. 7. Van Stavern GP, Bhatt A, Haviland J, Black EH. A prospective study assessing the utility of Cogan’s lid twitch sign in patients with isolated unilateral or bilateral ptosis. J Neurol Sci. 2007; 256(1Y2):84-85. 8. Osserman KE, Kaplan LI. Rapid diagnostic test for myasthenia gravis: increased muscle strength, without fasciculations, after intravenous administration of edrophonium (Tensilon) chloride. J Am Med Assoc. 1952; 150(4):265Y268. 9. Odel JG, Winterkorn JM, Behrens MM. The sleep test for myasthenia gravis: a safe alternative to Tensilon. J Clin Neuroophthalmol. 1991; 11(4):288. 10. Benatar M. A systematic review of diagnostic studies in myasthenia gravis. Neuromuscul Disord. 2006; 16:459-467. 11. Padua L, Stalberg E, LoMonaco M, et al. SFEMG in ocular myasthenia gravis diagnosis. Clin Neurophysiol. 2000; 111:1203-1207. 12. Lee JJ, Koh KM, Kim US. The anti-acetylcholine receptor antibody test in suspected ocular myasthenia gravis. J Ophthalmol. 2014; 2014:689792. 13. Roh HS, Lee SY, Yoon JS. Comparison of clinical manifestations between patients with ocular myasthenia gravis and generalized myasthenia gravis. Korean J Ophthalmol. 2011; 25(1):1-7. 14. Tung CI, Chao D, Al-zubidi N, et al. Invasive thymoma in ocular myasthenia gravis: diagnostic and prognostic implications. J Neuroophthalmol. 2013; 33(3):307-308. 15. Son SM, Lee YM, Kim SW, Lee OJ. Localized thymic amyloidosis presenting with myasthenia gravis: case report. J Korean Med Sci. 2014; 29(1):145-148. 16. Chapman KO, Beneck DM, Dinkin MJ. Ocular myasthenia gravis associated with thymic amyloidosis. J Neuroophthalmol. Epub ahead of print 2015 Mar 27. 17. Anthony SA, Thurtell MJ, Leigh RJ. Miller Fisher syndrome mimicking ocular myasthenia gravis. Optom Vis Sci. 2012; 89(12):e118-123. 18. Coombs PG, Mitchell J, Lelli G, Dinkin MJ. A case of silent sinus syndrome caused by a dacryocystorhinostomy presenting as myasthenia gravis. North American Neuro-ophthalmology Society. 2014; Abstract 91. 19. Saffra N, Rakhamimov A, Saint-Louis LA, Wolintz RJ. Acute diplopia as the presenting sign of silent sinus syndrome. Ophthal Plast Reconstr Surg. 2013; 29(5):e130Y-131. 2015 Subspecialty Day | Neuro-Ophthalmology “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 diplopic after an intervention forces them to switch fixation to their previously amblyopic eye. Treatment typically involves restoration 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. Section III: Double Vision and Nystagmus 41 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? Gregory P Van Stavern MD Final Diagnosis Suprasellar meningioma compressing the intracranial optic nerve and optic chiasm, causing a junctional scotoma Teaching Point 1 The visual field is one of the most important tools in the ophthalmologist’s armamentarium, as it allows precise localization of pathology within the afferent visual pathways. The retinal nerve fiber layer is highly topographically organized, and that topography is preserved throughout the visual pathway: a lesion anywhere from the retina to the primary visual cortex will cause predictable visual field defects, which can then narrow the differential diagnosis of the patient’s visual complaints and guide diagnostic workup. Visual field testing by perimetry should be performed in any patient with unexplained visual loss and is a key element in monitoring patients with known disease such as glaucoma and idiopathic intracranial hypertension. All perimetry methods are prone to inter-test variability, interoperator variability, and performance failures, and should be interpreted in the context of the entire examination and the results of confrontation testing. Indeed, careful confrontation perimetry can be a great ally, as a completely normal confrontation field (particularly when tested using a small red target) is inconsistent with extensive visual field loss seen on automated or kinetic perimetry, and should raise suspicion of artifact or performance issues. Patterns of visual field loss are highly localizing, so accurate interpretation relies upon basic knowledge of visual pathway neuroanatomy. In particular, the vertical meridian should be carefully examined. The optic chiasm is the anatomic substrate for the vertical meridian, and any visual field defect that respects the vertical midline raises concern for a chiasmal or retrochiasmal lesion. Automated static perimetry is probability-based, and the defects seen are not always as clean or “pretty” as those seen with kinetic perimetry, so it is important to review the field carefully to see if there is any portion of the defect that lines up along the vertical midline, even if there is some apparent crossover on the probability plots. When interpreting any visual field, it is helpful to ask the following questions: 1. 2. 3. 4. 5. Is the test reliable? Is the test normal? Does the visual field defect involve one eye or both eyes? If both eyes, does the defect respect the vertical meridian? If the defects respects the vertical meridian, is it bitemporal or junctional (optic chiasm) or homonymous (retrochiasmal)? Sellar and suprasellar tumors may cause intracranial optic nerve as well as chiasmal compression. Therefore, with such tumors it is not rare to see visual field defects that reflect optic nerve, chiasmal, and optic tract compression, and interpreting these defects can be challenging. Lesions that affect the anterior angle of the chiasm and the distal optic nerve produce a junctional scotoma, a distinct syndrome characterized by an optic nerve-related defect in the eye ipsilateral to the tumor, and a superotemporal defect in the eye contralateral to the mass. The contralateral temporal visual field defect is usually superotemporal (reflecting the inferonasal crossing fibers) but may be a complete temporal hemianopia. The origin of the superotemporal, contralateral visual field defect is of both historical and clinical interest. Wilbrand proposed that crossed fibers originating from ganglion cells inferior and nasal to the fovea in the contralateral eye extend anteriorly (< 2 mm) into the involved optic nerve and are thus subject to compression. This anatomic configuration is known as “Wilbrand’s knee.” Although some believe that Wilbrand’s knee is simply a pathologic artifact rather than a true anatomic structure, its clinical relevance remains unquestioned, and the finding of a “junctional” visual field defect provides strong evidence of a lesion at the anterior angle of the chiasm, mandating neuro imaging. Neuroimaging is indicated for all patients suspected of having a compressive optic neuropathy. The ideal modality is MRI of the brain, with and without gadolinium, with fat-saturated orbital views. This offers superb views of the globe, optic nerve head, optic nerve sheath, extraocular muscles, and orbital apex. It is also superior to CT for the evaluation of the intracanalicular and intracranial optic nerve, the pituitary fossa, and the cavernous sinuses. Treatment is dependent upon the specific type of tumor and the location, size, and degree of optic nerve dysfunction. The prognosis for visual outcome is related in part to duration of compression, as well as retinal ganglion cell and retinal nerve fiber layer integrity. Patients with severe optic atrophy at presentation (indicating loss of neurons and axons) have a worse prognosis for recovery, although some of these patients may have partial improvement after decompression. Teaching Point 2 The diagnosis of “previous NAION” should be used with caution unless the patient had documented optic nerve swelling at presentation and a history and subsequent clinical course compatible with that diagnosis. It is important to remember that NAION is ultimately a clinical diagnosis, supported by features such as acute onset, optic disc swelling, presence of a small, crowded optic disc, and subsequent stabilization with spontaneous resolution of optic disc edema. There are several “red flags” in the history and examination that suggest a diagnosis other than a previous episode of NAION: 1. 2. 3. 4. 5. No documentation of a swollen optic disc Gradual rather than acute onset Lack of a small, crowded optic disc (cup-to-disc < 0.2) Visual field defect that respects the vertical meridian Progression of vision loss in the absence of disc swelling Section IV: Test Interpretation 2015 Subspecialty Day | Neuro-Ophthalmology The ophthalmologist should have a high index of suspicion for a compressive optic neuropathy in such patients, for the following reasons: 1. Early detection of a mass may result in better prognosis for vision and survival (if neoplastic). 2. In many cases, the mass lesion may pose a risk to the unaffected eye. 3. Visual loss may recover once the compressive lesion is treated. Indeed, compressive optic neuropathies are among the most treatable forms of optic nerve dysfunction, and dramatic recovery may occur with decompression of the visual pathways. Therefore, early detection is critical, as the visual loss may be reversible. The presence of a junctional scotoma in this case strongly indicated that a compressive lesion was present. Selected Readings 1. Volpe NJ. Compressive and infiltrative optic neuropathies. In: Walsh and Hoyt’s Clinical Neuro-Ophthalmology, 6th ed. Philadelphia: Lippincott Williams and Wilkins; 2005:385-430. 2. Foroozan R. Chiasmal syndromes. Curr Opin Ophthalmol. 2003; 14(6):325-331. 3. Horton J. Wilbrand’s knee of the primate optic chiasm is an artefact of monocular enucleation. Trans Am Ophthalmol Soc. 1997; 95:131. 4. Lee AG, Chau FY, Golnik KC, et al. The diagnostic yield for the evaluation of isolated unexplained optic atrophy. Ophthalmology 2005;112:757-759. Should I Trust My Exam, or the OCT? 2. Retinal nerve fiber layer and macular OCT (segmentation) When interpreting the OCT, it is important to review not only the retinal nerve fiber layer but the macular thickness maps and the individual cross-sectional images. The thickness of the retinal nerve fiber layer is influenced by not only the integrity of the axons of the ganglion cells but glial cells and blood vessels.2 The macular thickness map and retinal segmentation can provide valuable information regarding the anatomical / structural status of the different layers of the retina. Certain disease processes have a predilection for particular layers of the retina. For example, retinal artery occlusion causes thinning of the inner layers of the retina, and acute macular neuroretinopathy (AMNR) affects the outer retinal layers.3 Furthermore, it has been shown that macular OCT findings can aid in differentiating postacute retinal artery occlusion from nonacute optic neuropathies. Ghazi et al performed a retrospective OCT study of 17 eyes with postacute retinal artery occlusion and 32 eyes with nonacute optic neuro pathy.4 They found 3 main features that distinguished postacute retinal artery occlusion from nonacute optic neuropathy: 1. Complete inner retinal atrophy with loss of the normal stratification of the inner retinal layers 2. Loss of the normal foveal depression 3. Marked thinning of the involved retina compared to nonacute optic neuropathy Furthermore, Dolan et al demonstrated that macular thinning was more profound in eyes with retinal artery occlusion than in eyes with nonarteritic anterior ischemic optic neuropathy.5 Improved resolution with currently available spectral domain OCT allows for the segmentation of the various layers of the retina, 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. M Tariq Bhatti MD References Final Diagnosis 1. Newman NJ. Optic disc pallor: a false localizing sign. Surv Ophthalmol. 1993; 37(4):273-282. Branch retinal artery occlusion with secondary optic nerve atrophy. 2. Kardon RH. Role of the macular optical coherence tomography scan in neuro-ophthalmology. J Neuroophthalmol. 2011; 31(4):353-361. Teaching Points 3. Fawzi AA, Pappuru RR, Sarraf D, et al. Acute macular neuroretinopathy: 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 cases of optic nerve pallor are due to primary optic nerve pathology.1 Retinal dystrophies (in particular cone dystrophies), retinal degenerations (ie, retinitis pigmentosa), and retinal artery occlusions can all result in secondary optic nerve pallor. In some cases, especially if nonacute, it can be clinically challenging to differentiate primary optic nerve pallor from secondary optic nerve pallor. Prior to the development of OCT, intravenous fluorescein angiography and electrophysiology, in addition to the clinical examination, were required. The addition of OCT to the armamentarium of paraclinical tests allows for quick identification of retinal pathology that otherwise might be below the threshold of funduscopic examination.2 43 4. Ghazi NG, Tilton EP, Patel B, Knape RM, Newman SA. Comparison of macular optical coherence tomography findings between postacute retinal artery occlusion and nonacute optic neuropathy. Retina 2010; 30(4):578-585. 5. Dotan G, Goldenberg D, Kesler A, Naftaliev E, Loewenstein A, Goldstein M. The use of spectral-domain optical coherence tomography for differentiating long-standing central retinal artery occlusion and nonarteritic anterior ischemic optic neuropathy. Ophthalmic Surg Lasers Imaging Retina. 2014; 45(1):38-44. 44 Section IV: Test Interpretation “I can’t get cocaine drops in my office!” Heather E Moss MD PhD Final Diagnosis Small cell lung cancer of the right lung apex causing right Horner syndrome Teaching Points 1. Physical exam findings are free and quick tests that guide the differential diagnosis of ptosis and anisocoria and can be diagnostic of Horner syndrome. 2. Eye drop testing is helpful to confirm an equivocal diagnosis of Horner syndrome or in a patient where neuroimaging evaluation poses risks. 3. The most important reason to diagnose Horner syndrome is to prompt workup for treatable etiologies: a. If recent medical history provides an etiology, no additional testing may be needed. b. Imaging of the sympathetic chain will screen for lesions causing Horner syndrome. Selected Readings 1. Almog Y, Gepstein R, Kesler A. Diagnostic value of imaging in Horner syndrome in adults. J Neuroophthalmol. 2010; 30:7-11. 2. Davagnanam I, Fraser CL, Miszkiel K, Daniel CS, Plant GT. Adult Horner’s syndrome: a combined clinical, pharmacological, and imaging algorithm. Eye 2013; 27:291-298. 3. Trobe J. The evaluation of Horner syndrome. J Neuroophthalmol. 2010; 30:1-2. “The MRI is abnormal; now what?” Fiona E Costello MD Diagnosis Repeat review of the MR-venogram reveals the diagnosis of cerebral venous sinus thrombosis as the cause of the patient’s seizures and manifestations of raised intracranial pressure. Teaching Points Cerebral venous sinus thrombosis (CVST) is a form of stroke whereby thrombosis occurs in the cerebral venous sinuses or veins.1 The incidence of CVST has been estimated at 3 to 5 cases per million population per year, representing 0.5%- 1% of all strokes.1 This condition tends to affect individuals aged less than 50 years, and is 3 times more common in women than men.1 CVST frequently affects patients with underlying risk factors for venous clot formation, including pregnancy, oral contraceptive pill use, systemic disease (eg, Crohn disease), infection (eg, mastoid sinus disease), and malignancy.1-2 The clinical features of CVST may vary and evolve over time. Thrombosis or stenosis of cerebral venous sinuses results in intracranial venous hypertension, which causes raised intracranial pressure by reducing passive cerebrospinal fluid resorption 2015 Subspecialty Day | Neuro-Ophthalmology through the arachnoid villi.3 Venous hypertension is common in CVST patients, who often manifest symptoms and signs of raised intracranial pressure including headaches, papilledema, and altered mental status.3 Additional features on examination may include cranial nerve palsies, focal neurological deficits, seizures, encephalopathy, and coma.2 Radiographic features of CSVT depend largely on the imaging modality utilized. Noncontrast computed tomography (CT) imaging of the head may show venous hemorrhage or infarction.2 Occasionally hyperdense signal changes within the affected sinus may be identified.2 With contrast administration and CT venography, a filling defect in a sinus may be seen. MRI may show venous thrombosis that is isointense on T1- and hypointense on T2-weighted imaging, thus mimicking a “flow void”; subacute venous blot may become hyperintense on T1-weighted imaging. Notably, 2-D time-of-flight MR-venography is routinely performed in suspected cases, albeit contrast MR venography is generally more sensitive in detecting CVST. Although digital subtraction angiography has historically been the gold standard, the relative lack of experienced angiographers and the invasive nature of the examination has led to a dramatic decline in its use.2 Despite major improvement in MRI techniques over the past decade, misinterpretation of brain MRI resulting in delayed diagnosis of CVST remains common.3 Imaging of the intracranial venous system with MR-venography is not systematically requested by many clinicians evaluating patients with a syndrome of isolated raised intracranial pressure, and radiologists are often asked to “rule-out CVST” on an isolated brain MRI.3 This may lead to false negative results. For the general ophthalmologist, CT or MR venography techniques are useful in the evaluation of patients with suspected raised intracranial pressure, particularly for those with atypical clinical features. In the case presented, the patient was obese, but her weight loss, underlying comorbidities, and seizures argued against the diagnosis of 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 minimal or no symptoms and an uneventful recovery (~65%), whereas others have a fulminant course culminating in extensive venous infarction, blindness, dependency, or death (~20%).2 Interventional neuroradiologists can perform catheter-directed thrombolysis by using targeted thrombolytics in the affected sinuses. As expected, hemorrhagic venous infarcts and coexisting malignancy correlate with poor outcome.2 Deep cerebral venous thrombosis also has a negative impact on prognosis due to what is often bilateral involvement of the thalami.2 Dural arteriovenous fistula and increased cerebrospinal fluid pressure can also lead to long-term complications after cerebral venous thrombosis.2 References 1. Amoozegar F, Ronksley PE, Sauve R, Menon B. Hormonal contraceptives and cerebral venous thrombosis risk: a systematic review and meta-analysis. Front Neurol. Published online 2015 Feb 2. doi: 10.3389/fneur.2015.00007. 2. Di Muzio B, Gaillard F, et al. Cerebral venous thrombosis. Radiopaedia. N.d. Available at: http://radiopaedia.org/articles/cerebralvenous-thrombosis. 3. Ridha MA, Saindane AM, Bruce BB, et al. MRI findings of elevated intracranial pressure in cerebral venous thrombosis versus idiopathic intracranial hypertension with transverse sinus stenosis. Neuroophthalmol. 2013; 37(1):1-6. 2015 Subspecialty Day | Neuro-Ophthalmology Everyone’s ESR Is High: Who Needs a Biopsy? Todd Alan Goodglick MD Final Diagnosis Giant cell arteritis Teaching Points The diagnosis of giant cell arteritis (GCA) is straightforward in textbook cases where an elderly patient presents with temporal headache, scalp tenderness, classic jaw claudication (ie, crescendo pain with chewing), and sudden loss of vision. However, this diagnosis comes up far more frequently in the differential diagnosis for variations of these symptoms such as atypical headache, transient vision loss, double vision, or even the incidental finding of an elevated sedimentation rate, platelet count, or C-reactive protein. This of course is particularly true when trying to make the diagnosis early to prevent the dreaded outcome of permanent vision loss (incidence in GCA is 15%-30% of cases). Eye doctors in particular need to maintain a high level of vigilance, as 20% of GCA patients present with only ophthalmologic complaints. What is known is that GCA is an inflammatory vasculopathy involving medium and large arteries including branches of the external carotids; ophthalmic, vertebral, and distal subclavian arteries; and thoracic aorta. There is an association with the disease polymyalgia rheumatica (PMR), which may pre- or postdate the diagnosis of GCA and cause diffuse myalgias of the neck and proximal extremities. About 50% of GCA patients will also attain a diagnosis of PMR at some point. PMR is 10 times as common as GCA, so PMR cannot be a highly specific risk factor for GCA even though a diagnosis of PMR often raises such a concern. Similarly, ethnicity can be used only as a relative risk factor, with the incidence in northern European whites twice as high as those of southern European descent and 20 times that in patients of Asian and African descent.1 Because of the lack of knowledge about the etiology of the disease or until there are sensitive and specific biomarkers for disease activity, there will always be ambiguous cases. The sensitivity of an elevated age-corrected sed rate (Westergren erythrocyte sedimentation rate (ESR) (age + 10 for men or age divided by 2 for women) in biopsy-confirmed GCA has been estimated at 84%; and that for elevated C-reactive protein (CRP), 86%. The specificity of these values was low, measuring 30% for either. Furthermore, only 4% of biopsy-proven patients had a normal value for both. Put another way, a high ESR is a nonspecific indicator of inflammation, and a normal ESR is reported in up to 20% of cases of GCA. The combination of elevated ESR and CRP has a sensitivity of 98%. The odds ratio predicting a positive temporal artery biopsy was 5 times for an elevated CRP, 4 times greater for thrombocytosis, and 1.5 times greater for an elevated ESR.2 However, these numbers (and all such statistics in this disease) are truly applicable only in a population with a proven diagnosis as opposed to the population encountered in clinical settings with variably suspicious symptoms. Clinicians are thus justifiably confused when it comes to ruling in or out a diagnosis of GCA. In all cases the diagnosis of GCA is best made, when possible, histologically rather than clinically. Even in the most typical clin- Section IV: Test Interpretation 45 ical scenarios the specificity of a pathology-supported diagnosis carries significant weight when the risks of prolonged steroid treatment are considered or encountered months later. A positive 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 known as this number would also depend on standardizing a “pretest” population of patients with respect to suspicious symptoms and signs of the disease and an alternative gold standard for the diagnosis. Without a better understanding of the pathogenesis of the disease this is not presently available. What is known is that a specific size of biopsy specimen would be expected to increase the sensitivity as skip lesions of foci of inflammation are known to commonly occur. A length of a fixed biopsy > 1.5–2.0 cm has often been found to be associated with a higher positive rate. There is a trend to diminish the utility of a temporal artery biopsy due to the perception of a (probably overestimated) false negative rate.3 When properly done the false negative rate is, although unknown, believed to be low. A properly done biopsy involves obtaining a piece of artery, localized to the pain and about 2 cm long given the possibility of skip lesions of inflammatory foci, which are known to occur frequently. Positive results would include the presence of a mononuclear infiltrate throughout the wall of the muscular artery with characteristic but not mandatory giant cells and destruction of the internal elastic lamina. The presence of giant cells distinguishes GCA from non-giant cell arteritides such as ANCA-positive vasculitis. Findings suggestive of atherosclerotic changes would not be considered positive. A biopsy of the superficial temporal artery is a straightforward outpatient procedure. The notion of a substantial false negative rate for temporal artery biopsies thus needs to be interpreted with caution but (somewhat) limits the utility of such a result in ruling out the disease. A negative result in the presence of classic symptoms might be regarded as a false negative and treatment continued, but otherwise a negative result can be used as a strong indicator against this diagnosis and a positive result makes the diagnosis unquestionable. A negative result suggests more than an elimination of a diagnosis of GCA, and itself has a differential diagnosis.4 Part of the confusion about the diagnosis has arisen from the American College of Rheumatology diagnostic criteria for this disease, in which 3 of 5 criteria need to be met for a diagnosis, only 1 of which is a positive biopsy. These criteria, however, were created in order to differentiate the various vasculitides and are of limited use in typical clinical diagnostic situations.3 Simultaneous biopsy of both sides is not necessarily recommended routinely as it is thought to increase the yield of a positive diagnosis by 1%-4%. Biopsy of the second side should be considered if there is a significant degree of suspicion for the disease despite an initial negative biopsy, given the usefulness of a tissue diagnosis. Frozen section of the artery has an 18% false negative rate and cannot be relied upon.5 The approach should be “treat and then biopsy,” using response to steroids as a significant and highly typical clinical occurrence. The histologic findings are thought to persist for at least 2-3 weeks after initiation of steroids, with evidence that changes of healed arteritis may be found up to 1 year later. In conclusion, the difficulties in making the diagnosis of GCA stem from our present lack of understanding of the etiology and 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 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 devastating loss of vision that this disease can cause. References 1. Weyand CM, Goronzy JJ. Giant cell arteritis and polymyalgia rheumatica. 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 2015 Subspecialty Day | Neuro-Ophthalmology 47 Financial Disclosure Transparency through disclosure of relationships with companies is one step in the Academy’s process of ensuring that all its educational activities are fair, balanced, and not commercially biased. The Academy’s Board of Trustees supports the position that having a financial relationship should not restrict expert scientific, clinical or non-clinical presentation or publication or participation in Academy leadership or governance, provided that appropriate disclosure of such relationship is made. Similarly, it should not restrict participation in AAO leadership or governance, so long as appropriate disclosure is made. As an ACCME accredited provider of CME, the Academy seeks to ensure balance, independence, objectivity, and scientific rigor in all individual or jointly sponsored CME activities. All contributors to Academy educational and leadership activities must disclose all financial relationships (defined below) to the Academy annually. The ACCME requires the Academy to disclose the following to participants prior to the activity: • All financial relationships with Commercial Companies that contributors and their immediate family have had 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, patients. • Meeting presenters, authors, contributors or reviewers who report they have no known financial relationships to disclose. The Academy will request disclosure information from meeting presenters, authors, contributors or reviewers, committee members, Board of Trustees, and others involved in Academy leadership activities (“Contributors”) annually. Disclosure information will be kept on file and used during the calendar year in which it was collected for all Academy activities. Updates to the disclosure information file should be made whenever there is a change. At the time of submission of a Journal article or materials for an educational activity or nomination to a leadership position, each Contributor should specifically review his/her statement on file and notify the Academy of any changes to his/ her financial disclosures. These requirements apply to relationships that are in place at the time of or were in place 12 months preceding the presentation, publication submission, or nomination to a leadership position. Any financial relationship that may constitute a conflict of interest will be resolved prior to the delivery of the activity. Financial Relationship Disclosure For purposes of this disclosure, a known financial relationship is defined as any financial gain or expectancy of financial gain brought to the Contributor or the Contributor’s immediate family (defined as spouse, domestic partner, parent, child or spouse of child, or sibling or spouse of sibling of the Contributor) by: • Direct or indirect compensation; • Ownership of stock in the producing company; • Stock options and/or warrants in the producing company, even if they have not been exercised or they are not currently exercisable; • Financial support or funding to the investigator, including research support from government agencies (e.g., NIH), device manufacturers, and/or pharmaceutical companies; or • Involvement with any for-profit corporation that is likely to become involved in activities directly impacting the Academy where the Contributor or the Contributor’s family is a director or recipient Description of Financial Interests Category Code Description Consultant / Advisor C Consultant fee, paid advisory boards or fees for attending a meeting Employee E Employed by a commercial company Lecture Fees L Lecture and speakers bureau fees (honoraria), travel fees or reimbursements when speaking at the invitation of a commercial company Equity Owner O Equity ownership/stock options (publicly or privately traded firms, excluding mutual funds). Patents / Royalty P Patents and/or royalties that might be viewed as creating a potential conflict of interest 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 Institute: S CredentialProtection: O Kathleen B Digre MD None Eli Lilly & Company: S Neuro-ophthalmix: E,P Marc J Dinkin MD Leah Levi MD Alphabiocom: C None Mays A El-Dairi MD Grant T Liu MD Prana Pharmaceuticals: C None AbbVie: C Alnaylam: C Apsara Therapeutics: C,O Aquaporumab: P Chugai Pharmaceuticals: C EMD Serono: C Genzyme: C Mallinckrodt: S,C MedImmune: C Novartis Pharmaceuticals Corporation: S,C Teva Neuroscience: C Rod Foroozan MD Collin M McClelland MD Lundbeck: C None Courtney E Francis MD Neil R Miller MD None None Todd A Goodglick MD Heather Moss MD PhD None M Tariq Bhatti MD None Clearview Healthcare Partners: C Eli Lily & Company: S H Lundbeck A/S: C Illinois Society for Prevention of Blindness: S National Eye Institute: S Research to Prevent Blindness: S Guy V Jirawuthiworavong MD Nancy J Newman MD None Gensight: C Santhera: C Trius/Cubist: C Marie D Acierno MD None Anthony C Arnold MD None Rudrani Banik MD National Eye Institute: S Jeffrey Bennett MD PhD Novartis Pharmaceuticals Corp.: C,L Valerie Biousse MD GenSight: C Gabrielle R Bonhomme MD Lynn K Gordon MD PhD None Gena Heidary MD Randy H Kardon MD PhD None Department of Defense TATRC: S Medface: O National Eye Institute: S Novartis Pharmaceuticals Corp.: C Veterans Administration: S John J Chen MD Bradley J Katz MD None Axon Optics, LLC: O Pfizer, Inc.: O None Michael C Brodsky MD Sophia Mihe Chung MD Eli Lilly & Company: S Fiona E Costello MD None Sarita B Dave MD New York State Department of Health: S Lanning B Kline MD None Gregory S Kosmorsky DO None Jacqueline A Leavitt MD None Michael S Lee MD Jeffrey G Odel MD Bayer Healthcare Pharmaceuticals: C Regeneron Pharmaceuticals: C Paul H Phillips MD None Stacy L Pineles MD None John Pula MD Questor: C Jacinthe Rouleau MD Allergan: C 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 Alfredo A Sadun MD PhD Edison Pharmaceutical: S Stealth Peptides: S Peter J Savino MD None Harold E Shaw Jr MD Abbott Laboratories: O AbbVie: O Bristol Myers Squibb: O Johnson & Johnson Consumer & Personal Products Worldwide: O Novartis Pharmaceuticals Corp.: O Pfizer, Inc.: O S Tonya Stefko MD None Mitchell B Strominger MD None Prem S Subramanian MD PhD NASA: C National Eye Institute: S Novartis Pharmaceuticals Corp.: S US Department of Defense: S Gregory P Van Stavern MD None Nicholas J Volpe MD None Subspecialty Day Advisory Committee William F Mieler MD Genentech: C Donald L Budenz MD MPH Alcon Laboratories, Inc.: C Ivantis: C Faculty Financial Disclosures Jonathan B Rubenstein MD Alcon Laboratories, Inc.: C Bausch + Lomb: C,L R Michael Siatkowski MD National Eye Institute: S Nicholas J Volpe MD None Daniel S Durrie MD Abbott Medical Optics: S AcuFocus, Inc.: C,L,O,S Alcon Laboratories, Inc.: L,O,S Allergan: S Alphaeon: C,O Avedro: L,O,S Strathspey Crown LLC: C,L,O Wavetec: C,O,P Francis S Mah MD Abbott Medical Optics Inc.: L Alcon Laboratories, Inc.: C,S Allergan: C,L Bausch + Lomb: C,L CoDa: C ForeSight: C Imprimis: C Ocular Therapeutix: C,S Omeros: C PolyActiva: C Shire: C 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 AAO Staff Christa Fernandez None Ann L’Estrange None Melanie Rafaty None Debra Rosencrance None Beth Wilson None 49 50 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. 2015 Subspecialty Day | Neuro-Ophthalmology
