Rapid Fire: Disorders of Higher Visual Function

A. Mika Moy, OD, FAAO Diplomate, Anterior Segment Section Ghazal Naseri, OD Pam Satjawatcharaphong, OD, FAAO, FSLS Cheyenne Huber, OD, FAAO No financial disclosures for any speaker What’s the Opposite of Color Blind?

•A. Mika Moy, OD, FAAO •Diplomate, Anterior Segment Section Case

• 38 year old WF • CC: Sees colors for vowels and numbers 0123456789 – Recently discovered boyfriend does not – Wonders if this is a worrisome symptom – Has noticed this her whole life AEIOUY • Medical and Ocular history unremarkable • No meds, no allergies •No history of drug use Exam Findings

• VA s 20/20, 20/20 • Colors consistent • Color Vision: Normal • She is very particular about the shade • All other exam findings within • Font type, size, etc. does not change color normal limits • Only sees colors once she recognizes the word • E’s color changes depending on whether it is

silent or not Can you see colors now? now? colors see you Can Differential Diagnosis

• Developmental visual synesthesia • Easy to differentiate: – Grapheme-color variety – Acquired – Smallest meaningful unit in writing • Transient • Numbers, letters, etc. • Suggestible • Acquired synesthesia • Inconsistent – Side effect of psychoactive drugs – Temporal lobe tumor Psychoactive Drugs

• LSD – Lysergic Acid Diethylamide • Psilocybin – Found in some variety of mushrooms • Ayahusca – Used for religious purposes ancient Amazonian tribes

• 350 known psychoactive chemicals

• Transient Temporal Lobe Tumors/Epilepsy

• Hallucinations – Auditory – Visual – Olfactory – Gustatory – Tactile • Visual distortions – Macropsia – Micropsia • Synesthesia

• Transient Developmental Synesthesia

• One sensory input triggers another • Hundreds of combinations • Most common: – Grapheme: Color: 64% – Time-unit: Color 22% – Musical Sound: Color 18.5% • Many synesthetes have more than one – Vast majority of pairings include vision and color Developmental Synesthesia

• One sensory input triggers another sense • Hundreds of combinations • Most common: – Grapheme: Color: 64% – Time-unit: Color 22% – Musical Sound: Color 18.5% • 50% have more than one – Vast majority include vision and color – Movement, emotion, touch, temperature, time units, , flavor, odor, personality Developmental Synesthesia

• Begins early in life (approx. age 3) • Very consistent patters – Ex: what letter is what color • Most common type: grapheme by far – 40% A is red • Runs in families – F=M • Involuntary • Up to 24% of population

Rouw, Scholte. Neuropsychologia. 2016 Theories of Developmental Synesthesia • Increased Connectivity Theory • Faulty Inhibition Theory – Everyone born with it – “Normal” brain inhibits cross talk – Dissipates for most – Synesthetes brain does not – Brain connections pruned as a function of time • Ex: Non-synesthetes can have occasional synesthesia • Ex: Newborns: sound evokes – Meditation response in – Drugs • But: synesthesia doesn’t appear – While falling asleep until childhood

Increased white matter connectivity in grapheme color synesthesia What if you are color deficient?

• Case report –S-cone deficient male – Grapheme color synesthete – “Martian colors” – Never saw in the real world

Ramachandran & Hubbard, J. Consciousness Studies, 2001 Remember…the DRESS Color Not Just Photoreceptors Increased Interest and Research

• No association with or • Identify Genetic Loci migraine with – Tends to run in families – Both exhibit hyperexcitability of • Connection with Autism? visual cortex – Color Measures • Improved in synesthetes • Decreased in migraineurs Jonas. . 2015 • 18.9 % synesthetes subjects with • Autism associated with autism (n=164) – Decreased long-range neuro- • 7.2% synesthetes in neurotypical connectivity controls (n=97) – Increased short range

• Only tested for • Perfect pitch associated with – Grapheme – color – Autism – Sound – color – Synesthesia Benefits/Drawback of Synesthesia

• Most feel beneficial or neutral How many 2s are there?

• Often helps with memory • Increased intelligence • Increased emotionality • Increased openness

• Increased neuroticism • Decreased conscientiousness Benefits/Drawback of Synesthesia

• Most feel beneficial or neutral

• Often helps with memory • Increased intelligence • Increased emotionality • Increased openness

• Increased neuroticism • Decreased conscientiousness Back to Our Patient

• She is not bothered if this is normal • Benefits – Remembers people’s names easily • Associates with color • Drawbacks –Distracted reading Take Home Points: • Synesthesia is cross talk between two • It is a perceptual phenomenon • There are hundreds of sense parings in synesthesia - The vast majority involve vision and color • Research in this area is ongoing and increasing - Genetics - Autism • Synesthetes are rarely bothered and no treatment is indicated • If acquired and not consistent, a neuro consult may be indicated VISUAL SNOW SYNDROME

Ghazal Naseri, O.D. University of California- Berkeley School of Optometry Case Presentation

• 25-year-old Caucasian Male • CC: visual changes/fluctuations since 2015; vision appears like “TV static” • (+) light sensitivity • (+) migraine headaches • Ocular history: unremarkable • Medical History: spinal injury November 2011 • No medication/drugs/tobacco/KDA Clinical Findings

• BCVA 20/20 OD&OS

• Pupils: PERRL; (-) APD

• Color vision normal OD &OS with HRR

• Confrontational exam: unremarkable

• Ophthalmic exam findings unremarkable with dilated exam OD&OS

• Last brain MRI in late 2018 unremarkable; was cleared by his neurologist for any neurological findings Fundus Photos

Fig 1. Posterior pole of patient’s right eye Fig 2. Posterior pole of patient’s left eye Humphrey 30-2

Fig 3. HVF 30-2; Left eye Fig 4. HVF 30-2; Right eye Differential Diagnosis

Visual Snow Syndrome Migraine with Aura Hallucination Persisting Perception Disorder Visual Snow Syndrome • Clinical diagnosis based on visual symptoms reported by patient with no existing ocular or neurological pathologies

• Symptoms described as small flickering dots mostly monochromatic but could be chromatic, similar to static signal of an analog television

• Onset usually in young adulthood with no gender predisposition

Fig 5. Normal vision vs. vision with visual snow 7 Diagnosis Criteria

• Presence of dynamic, continuous, tiny dots in the entire visual field lasting longer than 3 months in addition to at least 2 of the following symptoms: 1. 2. Enhanced entoptic phenomena 3. 4.

Schankin et al (2014). Brain, 137, 1419–1428. Puledda, F. et al. , 10.1212 (2020) Fig 7.a) normal vision b) visual snow c) palinopsia d) enhanced entoptic phenomena and photophobia e) nyctalopia f) combination of b-d 6 Other Associated Conditions

• Migraine

•

• Balance issues

• , Anxiety, tremor

Renze, M. International Tinnitus Journal , 21(1), 74–75. (2017) Metzler, A. Iet al,Current Neurology and Neuroscience Reports, Vol. 18. (2018) Pathophysiology

• Thalamocortical Dysrhythmia

• Cortical Hyperexcitability Thalamocortical Dysrhythmia • Imbalance between Koniocellular and Parvo/Magnocellular cells in lateral geniculate nucleus

• Mostly discussed in other conditions such as tinnitus, tremor, neurogenic pain, etc.

Fig 8. Diagram of visual pathways

Lauschke, J. L. et al. Journal of Clinical Neuroscience, 28, 123–127. (2016) Cortical Hyperexcitability

• Higher order disruption

• Pattern-reversal in visual evoked potential (VEP) • Hypermetabolism of lingual gyrus on PET scan • Functional hyperconnectivity in brain areas involved in form and motion processing, attention and working memory on fMRI

Fig 9. PET scan of VSS patient showing hypermetabolism in the ligual gyrus 6 Eren O. et al., Ann Neurol, 84:946–949. (2018) Schankin, C. J. et al. Headache, 54(6), 957–966.(2014) Traber, G. L. et al. Current Opinion in Neurology.(2019) Our Patient’s Symptoms

• (+) monochromic grayish dot over field of vision • (+) Palinopsia • (+) Photosensitivity • (+) h/o Tinnitus • (+) Migraine

Fig 10. VSS symptom survey 2 Management

• Patient education and support groups • Tinted lenses : mostly in blue-yellow spectrum • Oral medications

• Goal: alleviate the symptoms to a level that patients can be more functional Oral Medication

• Diuretics • NSAIDs - Acetazolamide • Ketamine - Furosemide • Topiramate • Antiplatelet agents • - Aspirin - Picotamide - - Divalproex sodium • Antidepressants - Carbamazepine - Tricyclic antidepressants • Calcium channel blockers/calcium • Triptan antagonist • Antipsychotics • Beta-blockers

Bou Ghannam, A. et al. Current Treatment Options in Neurology, Vol. 19. ( 2017) Oral Medication

1. Lamotrigine 2. Verapamil 3. Acetazolamide Visual snow syndrome is a clinical diagnosis based on presenting symptoms and normal ocular and neurological findings. There are set criteria proposed for diagnosis of VSS.

Theories for underlying cause include Take Home Points thalamocortical dysrhythmia and cortical hyperexcitability.

Management options include patient education, support groups, tinted lenses and oral medication.. & Visual Aura: Should We Be Concerned?

Pam Satjawatcharaphong, OD, FAAO, FSLS MIGRAINE PREVALENCE

• Migraine impacts 15-20% of the general adult population – 17-25 % of women – 6-10% of men

• 25-30% of migraineurs experience aura – ~5% of the general adult population

• Highest prevalence of migraine is amongst persons 20 to 50 years of age – Can start in childhood - rare MIGRAINE CLASSIFICATION INTERNATIONAL CLASSIFICATION OF HEADACHE DISORDERS (ICHD), 2018 MIGRAINE WITHOUT AURA INTERNATIONAL CLASSIFICATION OF HEADACHE DISORDERS (ICHD), 2018 Diagnostic Criteria

A. At least five attacks fulfilling criteria B–D

B. Headache attacks lasting 4-72 hours (when untreated or unsuccessfully treated)

C. Headache has at least two of the following four characteristics: 1. unilateral location 2. pulsating quality 3. moderate or severe pain intensity 4. aggravation by or causing avoidance of routine physical activity (e.g. walking or climbing stairs)

D. During headache at least one of the following: 1. nausea and/or vomiting 2. photophobia and phonophobia

E. Not better accounted for by another ICHD-3 diagnosis. MIGRAINE WITH AURA INTERNATIONAL CLASSIFICATION OF HEADACHE DISORDERS (ICHD), 2018 Diagnostic Criteria A. At least two attacks fulfilling criteria B and C

B. One or more of the following fully reversible aura symptoms: 1. Visual – most common type 2. Sensory 3. Speech and/or language 4. Motor 5. Brainstem 6. Retinal

C. At least two of the following four characteristics: 1. at least one aura symptom spreads gradually over 5 minutes, and/or two or more symptoms occur in succession 2. each individual aura symptom lasts 5-60 minutes 3. at least one aura symptom is unilateral 4. the aura is accompanied, or followed within 60 minutes, by headache

D. Not better accounted for by another ICHD-3 diagnosis, and transient ischemic attack has been excluded. CASE

• 32 year old white female presents for an urgent care visit

• Chief Complaint: Has had two recent episodes of “lights in her vision” • 1st episode: lights were “wavy”, “seemed to be in both eyes”, “looked like I was underwater in that area” • 2nd episode: lights were “bright and sparkly in a zigzag pattern” with “patchy loss of vision in the area” • Episodes had gradual onset, lasting between 20-30 minutes • This has not occurred in the past • No associated headache

• Medical and Ocular history: unremarkable

• Medications: Sprintec birth control

• NKDA

• No smoking, no recreational drug use EXAMINATION FINDINGS

• VA with low myopic correction: 20/15 OD & OS

• Pupils: PERRL, (-) APD

• EOMS: Full

• Anterior Segment: Unremarkable

• Posterior Segment: Unremarkable

• IOP with Goldmann: 14/14 mmHg

• FDT: No defects DIFFERENTIAL DIAGNOSIS

• Visual Aura Without Migraine

• Transient Ischemic Attack (TIA)

• Posterior Vitreous Detachment

• Retinal Detachment TIA VS. VISUAL AURA WITHOUT HEADACHE • TIA can be difficult to differentiate from visual aura without headache

• In the absence of a headache, patients will often first present to an eye care professional with visual symptoms only

• Thorough case history can help distinguish • Unilateral or bilateral? • Still present with eyes closed? • Absence of vision vs. presence of image (negative or positive visual symptoms)? • Shape? • Sudden vs. gradual onset? • Spread or intensifies over time? • Duration? • History of past episodes? • Presence of other neurologic symptoms? • Concurrent cardiovascular disease? TIA VS. VISUAL AURA WITHOUT HEADACHE PAEMELEIRE, CASE-BASED DIAGNOSIS & MANAGEMENT OF HEADACHE DISORDERS, 2014 TIA VS. VISUAL AURA WITHOUT HEADACHE DENNIS & WARLOW, JOURNAL OF NEUROLOGY, NEUROSURGERY & PSYCHIATRY, 1992 • Examined 50 migraine aura w/o HA and 50 TIA patients, similar demographics

• Aura group much more likely to report a more gradual onset of symptoms which spreads or intensifies over a periods of minutes (not seconds), and in typical fortification spectrum pattern

• TIA group symptoms more acute onset

• Aura group had very low risk of developing serious vascular complications even in the presence of existing vascular disease, so worth distinguishing from TIA which has higher risk of complication/death TRANSIENT ISCHEMIC ATTACK (TIA)

• About 1 in 3 people who has a TIA will eventually have a stroke, with about half occurring within one year after the TIA.5

• Though TIA presents a higher risk of stroke, migraine with aura, has consistently been identified as an independent risk factor for ischemic stroke. 11

• Clinical observations as well as recent experimental data, suggest that migraine aura exists on a continuum of hypoperfusion disorders that includes transient ischemic attacks and cerebral infarcts.11 VISUAL AURA

• Most common type – over 90% of patients with aura • Can occur without headache

“Fortification spectrum”: a zigzag figure near the point of fixation that may gradually spread right or left and assume a laterally convex shape with an angulated scintillating edge, leaving absolute or variable degrees of relative scotoma in its wake.1

Image Credit: Migraine Art Slideshow, 2008, Nytimes.com DIFFERENTIAL DIAGNOSIS

• Visual Aura Without Migraine Back to the patient: • 1st episode: lights were “wavy”, “seemed to be in both eyes”, “looked like I was underwater in that • Transient Ischemic Attack area” • 2nd episode: lights were “bright and sparkly in a zigzag pattern” with “patchy loss of vision in the area” • Posterior Vitreous Detachment • Episodes had gradual onset, lasting between 20- 30 minutes • Retinal Detachment CORTICAL SPREADING DEPRESSION

Since its original description in 1944 by Leão, Cortical Spreading Depression (CSD) has been hypothesized to be the underlying mechanism of migraine aura. 6

Before or simultaneously with the onset of aura symptoms, regional cerebral blood flow is decreased in the cortex corresponding to the clinically affected area and often over a wider area. 1

Blood flow reduction usually starts posteriorly and spreads anteriorly, and is usually above the ischemic threshold. 1

Image Credit: Olesen et al, Lancet Neurol, 2009 CORTICAL SPREADING DEPRESSION

CSD susceptibility is modulated by multiple factors

Multiple risk factors may have additive effects in increasing cortical excitability 7

Image Credit: Dalkara et al, Lancet Neurol, 2010 AURA & ASSOCIATION WITH STROKE

• Migraine, particularly migraine with aura, has consistently been identified as an independent risk factor for ischemic stroke. 11

• Several population-based studies have shown patients with migraine with aura showed a two-fold increased risk of ischemic stroke. 1,11,12

• Mechanism of increased risk remains unclear

Etminam et al, BMJ, 2005 AURA & ASSOCIATION WITH STROKE MIGRAINE & CONTRACEPTION

Etminam et al, BMJ, 2005 AURA & ASSOCIATION WITH STROKE MIGRAINE & CONTRACEPTION OR SMOKING

Harriott and Barrett, Curr Neurol Neurosci Rep, 2015 THE ROLE OF THE OD IDENTIFY RISK FACTORS FOR STROKE

Modifiable risk factors that may amplify stroke risk:

• Two studies of young women with history of migraine and smoking: – Risk of 10.2 (95 % CI 3.5–29.9) – Risk of 7.39 (95 % CI 2.14–25.5)

• Two studies of young women with history of migraine and oral contraceptive use: – Risk of 13.9 (95 % CI 5.5–35.1) – Risk of 16.9 (95 % CI 2.2–106.0)

Harriott and Barrett, Curr Neurol Neurosci Rep, 2015 BACK TO OUR PATIENT

• Patient had been on estrogen & progesterone based oral contraceptive for 6 months (Sprintec)

• After visit had one more episode of visual aura without headache (3 total)

• Discussed with PCP and switched to progesterone only oral contraceptive

• Aura symptoms completely resolved after switch to new medication THE ROLE OF THE OD TAKE HOME POINTS

• Discuss with patients the low overall risk of stroke in patients with aura alone – The risk is higher with increasing frequency of migraine and if the aura does not include nausea and vomiting

• Smoking and oral contraceptives increases this overall risk several fold, so removing these modifiable risk factors can be beneficial

• Encourage visit with PCP to formulate a plan – Reduce migraine frequency by avoiding triggers (environmental/lifestyle change), or possibly medication – Switching birth control method such as IUD or progesterone formulation OC – Smoking cessation counseling – Management of cardiovascular disease, like HTN A Beautiful Mind: Charles Bonnet Syndrome Cheyenne Huber, OD, FAAO Case History

Ocular history Dry ARMD, pseudophakia; sees OMD every 3 months

Medical history Hypertension

Medications Lisinopril, Preservision; no drugs/tobacco/NKDA

Personal assessment Oriented time/person/place Low Vision Case History

Chief complaint Difficulty reading newspaper c magnifier

Living With supportive daughter

Hobbies Watch news, reading

Mobility Ambulates slowly, no fall history

Visual disturbance Sees image of plants Low Vision Case History

• “Often patients tell me they see things that aren’t really there. Have you ever noticed this?” – Yes! – In evenings, in her living room – Not bothersome, bright green – Go away when she gets up – Told her daughter Differential Diagnosis

• Hallucinations • Misperception • Entopic phenomena • Charles Bonnet Syndrome Differential Diagnosis: Hallucinations

• No corresponding sensory stimuli • Often multi-sensory involvement • Common causes – Drug use – Medication side effect – Psychiatric disorders – Neurologic/metabolic disease Differential Diagnosis: Misperception

• , distortion, dendropsia • Stimulus is present • Common causes – Ocular disease – Neurologic/psychiatric disease Differential Diagnosis: Entopic Phenomena

• Visual effects whose source is within the eye: – Flashes – – Aura – Blue light entopic phenomenon Differential Diagnosis: Charles Bonnet Syndrome

• The occurrence of visual hallucinations in visually impaired patients • Mentally healthy • Demonstrate insight into reality Differential Diagnosis: Case History

• Is there a diagnosis that causes visual impairment? • Are the images perceived to be real? • Any other atypical behavior? • Memory loss? • Confusion? Pertinent Findings

Best-corrected visual acuity with Bailey- 10/50 (20/100) OD, 10/160 (20/320) OS Lovie chart Contrast with Mars test 1.2 log

Berkeley Central Field Test (near tangent Central scotoma 2-6 degrees OD, OS screen) Reading acuity 0.20/1.6 M efficiency, EVP = +8.00D Diagnosis Codes

• H35.3130 Nonexudative age-related macular degeneration, bilateral, unspecified • H54.2x12 Low vision right eye cat 1, low vision left eye cat 2 • H53.72 Impaired contrast sensitivity • R44.1 Visual hallucinations Inclusion Criteria for Charles Bonnet Syndrome

• Changes in definition not only over time, but current definition depends on the field • Newer definitions in neurology may not require vision loss for diagnosis • Auditory symptoms more recently accepted within psychiatry Risk Factors

Sensory Visual Functions Age Deprivation • VA, contrast, • Acquired vision • Social isolation VF loss • Dark • 20/40 • Vascular environment • Monocular disease Risk Factors

Sensory Visual Functions Age Deprivation • VA, contrast, VF • Acquired vision • Social isolation • 20/40 loss • Dark • Monocular • Vascular environment disease Pathophysiology

Spontaneous or typically suppressed abnormal activity? Neurotransmitter Involvement

• Deregulation of dopamine response • Seratonin, acetylcholine involvement – depends on the location • Literature from psychiatry links with dementias and Parkinson’s disease Epidemiology

• Reports include 0.04-60% of patients with visual impairment • 15-30% of patients with AMD • Variation due to underreporting, inclusion criteria, and misunderstanding • < 50% of family medicine doctors are aware of CBS Image Features

• Vivid, high detail, in focus Description • Color or black & white

• Lasts seconds to minutes Timing • Daily or rarely

• Pleasant, annoying, neutral Response • Rarely frightening Image Classification

Simple •Colors, patterns, shapes Complex •Fully formed objects/scenes Typical •Only involves vision Atypical •Multisensory Prognosis

• Over-generalization based on case studies • Widely varied prognosis • No current agreed upon treatment • Consider quality of life Treatment and Management

• Treat vision loss and maximize visual function with low vision aids • +8.00D hand held magnifier • Change state • Patient reassurance with family, friends, and caregivers Treatment and Management

• Rule out neuropsychiatric, metabolic, or toxic causes • Antipsychotics, , antidepressant therapy Conclusion

• CBS occurs in cognitively normal patients with vision loss • Established diagnostic criteria may be changing • Medication treatment still being established • Optometrists are equipped to provide management and support to our patients and their families- ask your patients! • Refer for low vision services References • Cytowic, Richard. Synesthesia. The MIT Press, 2018. • Brang, D, Ahn, E. “Double-blind study of visual imagery in grapheme-color synesthesia” Cortex. 117 (89-95), 2019. • Jewasnski, J, et al. “The evolution of the concept of synesthesia in the nineteenth century as revealed through the history of its name.” J. of the History of the Neurosciences. 2019 DOI: 10.1080/0964704X.2019.1675422 • Jonas, C., Hibbard, P. “Migraine in Synesthetes and Nonsynesthetes: A Prevalence Study.” Perception. 44(10), 1179-1202. 2015. • Rouw, R., Scholte, S., “Personality and cognitive profiles of a general synesthetic trait.” Neuropsychologia. 88(35-48), 2016. • Safran, A., Sanda, N. “Color synesthesia. Insight into perception, emotion, and consciousness.” Curr Opin Neurol. 2015, 28:36-44. • Baron-Cohen, S., Johnson, D., Asher, J. et al. Is synaesthesia more common in autism?. Molecular Autism 4, 40 (2013). https://doi.org/10.1186/2040-2392-4-40 • Bou Ghannam, Alaa and Victoria S. Pelak. "Visual Snow: a Potential Cortical Hyperexcitability Syndrome." Current Treatment Options in Neurology. Vol. 19. 3. Current Science Inc., 1 3 2017. • Ciuffreda, Kenneth J. and Barry Tannen. "Visual Snow Syndrome (VSS): An Evolving Neuro-Optometric Clinical Perspective." Vision Development & Rehabilitation (2019): 75-82. • Metzler, Abby I. and Carrie E. Robertson. "Visual Snow Syndrome: Proposed Criteria, Clinical Implications, and Pathophysiology." Current Neurology and Neuroscience Reports. Vol. 18. 8. Current Medicine Group LLC 1, 1 8 2018. • Renze, Matthew. "visual-snow-syndrome-and-its-relationship-to-tinnitus." International Tinnitus Journal 21.1 (2017): 74-75. • Traber, Ghislaine L., Marco Piccirelli and Lars Michels. "Visual snow syndrome." Current Opinion in Neurology (2019): 1. • White, Owen B., et al. "Visual Snow: Visual Misperception." Journal of Neuro-Ophthalmology. Vol. 38. 4. Lippincott Williams and Wilkins, 2018. 514-521. • Headache Classification Committee of the International Headache Society (IHS). The International Classification of Headache Disorders, 3rd edition (beta version). Cephalagia 2013 Jul; 33(9):629-808. • Hill, Donna L. et al. Most Cases Labeled as ‘‘Retinal Migraine’’ Are Not Migraine. J Neuro-Ophthalmol 2007; 27:3–8. • Leão A, Spreading Depression of Activity in the Cerebral Cortex. Fed. Proc., 1944; 3:28. • Charles AC and Baca SM. Cortical spreading depression and migraine. Nature Reviews Neurology 2013 Nov; 9:637-644. • Olesen J, Burstein R, Ashina M, Tfelt-Hansen P. Origin of pain in migraine: evidence for peripheral sensitisation. Lancet Neurol 2009; 8: 679–90. • Dalkara T, Nozari A, and Moskowitz, M. Migraine aura pathophysiology: the role of blood vessels and microembolisation. Lancet Neurol. 2010 March; 9(3):309–317. • Olesen J, Larsen B, Lauritzen M. Focal hyperemia followed by spreading oligemia and impaired activation of rCBF in classic migraine. Ann Neurol 1981;9:344–52. References • Etminan M, Takkouche B, Isorna FC, Samii A. Risk of ischaemic stroke in people with migraine: systematic review and meta-analysis of observational studies. BMJ 2005;330:63. • Harriott A, Barrett K. Dissecting the Association Between Migraine and Stroke. Curr Neurol Neurosci Rep 2015;15:5. • Diener, H., Pfaffenrath, V., Pageler, L., Peil, H. and Aicher, B. (2005), The fixed combination of acetylsalicylic acid, paracetamol and caffeine is more effective than single substances and dual combination for the treatment of headache: a multicentre, randomized, double-blind, single-dose, placebo- controlled parallel group study. Cephalalgia, 2005;25: 776–787. • Diener, HC et al. Headache Classification by History has Only Limited Predictive Value for Headache Episodes Treated in Controlled Trials With OTC Analgesics. Cephalplegia 2008;29:188-193. • Tfelt-Hansen P, et al. Ergotamine in the acute treatment of migraine: A review and European consensus. Brain 2000;123(1):9-18. • Donnet A, et al. Ergot Use and Overuse: A Pharmacoepidemiology Retrospective Cohort Study. Headache 2016 Mar;56(3): 547-54. • Becker, WJ. Review Article: Acute Migraine Treatment in Adults. Headache 2015;55:778-793 • Aurora SK, et al. OnabotulinumtoxinA for chronic migraine: efficacy, safety, and tolerability in patients who received all five treatment cycles in the PREEMPT clinical program. Acta Neurol Scand 2014;129:61–70. • Lipton RB, et al. OnabotulinumtoxinA improves quality of life and reduces impact of chronic migraine over one year of treatment: Pooled results from the PREEMPT randomized clinical trial program. Cephalalgia 2016;36(9):899–908. • Amirlak B, et al. Anatomical Regional Targeted (ART) BOTOX Injection Technique: A Novel Paradigm for Migraines and Chronic Headaches. Plast Reconstr Surg Glob Open 2016;4:e1194. • Zhao L, et al. The Long-term Effect of Acupuncture for Migraine Prophylaxis: A Randomized Clinical Trial. JAMA Intern Med 2017. • Puledda F, Goadsby PJ. An Update on Non-Pharmacological Neuromodulation for the Acute and Preventive Treatment of Migraine. Headache 2017. • American Academy of Neurology. Guidelines for the Prevention of Stroke in Women: A Statement for Healthcare Professionals From the American Heart Association/American Stroke Association. Stroke 2014;45:1545-1588. • 1. Buyukgol H et al. Evaluation of the Clinical Features, Management, and Prognoses of Patients With Charles Bonnet Syndrome. The Journal of Nervous and Mental Disease 2019. Dec;207(12):1045-1047. • Pang L. Hallucinations Experienced by Visually Impaired: Charles Bonnet Syndrome. Optometry and Vision Science 2016;93(12):1466-1478. • Boller F et al. Charles Bonnet Syndrome and Other Hallucinatory Phenomena. Frontiers of Neurology and Neuroscience 2018;41:117-124. • Leandro JE et al. The Charles Bonnet Syndrome in Patients With Neovascular Age-Related Macular Degeneration:Association With Proton Pump Inhibitors. Investigative Ophthalmology and Vision Science 2017;58(10):4138-4142. • Carpenter K, Jolly JK, Bridge H. The elephant in the room: understanding the pathogenesis of Charles Bonnet syndrome. Ophthalmic and Physiological Optics 2019;39:414–421. • Gordon, K and Felfeli, T. Family physician awareness of Charles Bonnet syndrome. Family Practice, 2018;35(5):595-598. Disorders of Higher Visual Function

A. Mika Moy, OD, FAAO Diplomate, Anterior Segment Section Ghazal Naseri, OD Pam Satjawatcharaphong, OD, FAAO, FSLS Cheyenne Huber, OD, FAAO

Thank you!