2015 NORTHWEST RESIDENTS CONFERENCE Pacific University College of – Jefferson 224 Friday, June 12 & Saturday, June 13, 2015

PROGRAM AGENDA

Faculty: Carole Timpone, OD, FAAO, FNAP, Associate Dean of Clinical Programs and Director of Residencies, will oversee the event. Each resident will deliver a 30 minute presentation that includes responding to questions and comments from attendees.

FRIDAY, JUNE 12, 2015 PAGES Rachael Lloyd, OD 1-11 Idiopathic Intracranial Hypertension – You Down VA Puget Sound Health Care System with PTC? Alisa Nola, OD Post Trauma Vision Syndrome Diagnosis and 12-21 Bright Eyes Vision Clinic Management using Visual Evoked Potentials (VEP) Mackenzie Macintyre, OD Ocriplasmin for Vitreomacular Adhesion: Boom 22-32 VA Portland Health Care System and Bust? Emily Liu, OD Plaque to the Future: Utilizing SD-OCT in the 33-41 VA Puget Sound Health Care System Management of CRAO and Retinal Emboli BREAK Haley McCoy, OD Ocular Sequelae of Common Systemic 42-50 VA Portland Health Care System Magi Labib, OD Retinal Artery Occlusions Secondary to Illicit Drug 51-60 Lebanon VA Medical Center Use Victoria Roan, OD Oral Acetazolamide versus Topical Dorzolamide in 61-69 Jonathan Wainwright Memorial VAMC the Treatment of Pigmentosa Kolten Kuntz, OD A Look into Current Trends and Future Advances in 70-76 Spokane VA Medical Center Surgery Frank Zheng, OD The Effects of Decentering Multifocal Soft Contact 77-87 Pacific University and Associated Clinics Optics and its Relation to Distance Vision Warren Whitley, OD 88-98 Differential Diagnoses of Post-Operative Eye Care Associates of Nevada SATURDAY, JUNE 13, 2015 Crystal Thanos, OD Ocular Indications for Carotid Imaging 99-108 Roseburg VA Medical Center Branden McFadden, OD Using Ocular Coherence Tomography for Analysis 109-116 Spokane VA Medical Center of Peripheral Retinal Findings Stacy Hill, OD Bilateral Congenital Superior Oblique Palsy 117-127 Pacific University and Associated Clinics Rachel Lee, OD Case-series of Homonymous or Altitudinal 128-135 VA Portland Health Care System Hemianopia Management Using the Prism Connie Lee, OD Congenital – New Ideas on Treatment 136-143 Vision Northwest BREAK Truyet Tran, OD Cystoid : A Case Report and Review 144-154 VA Portland Health Care System Gleb Sukhovolskly, OD The Effects of Exogenous and Endogenous Jonathan Wainwright Memorial VAMC 155-164 Corticosteroids on Pathophysiology of Central Serous Choriorentiopathy Shannon Currier, OD Understanding Choroidal Folds 165-175 VA Portland Health Care System Janice Pierce, OD Ocular Sequelae of Cranial Nerve Palsies 176-195 VA Southern Oregon Keegan Bench, OD Retrograde Degeneration of Retinal Ganglion Cells Spokane VA Medical Center 196-210 Detected with Optical Coherence Tomography in Patients with Homonymous Hemianopia

This program is sponsored in part by an unrestitrict ed ed uca tiona l gran tft from

2015 NORTHWEST RESIDENTS CONFERENCE 6/5/2015

LEARNING OBJECTIVE

 By the end of this course, attendees will be able to recognize and provide an overview of the diagnosis, testing, treatment, and management of idiopathic intracranial hypertension. Two case studies will be reviewed. IDIOPATHIC INTRACRANIAL HYPERTENSION –YOU DOWN  Learning objectives  Definition of IIH WITH PTC?  Diagnosis Diagnosis, management, and treatment – Two cases  Pertinent testing Rachael Lloyd, O.D.  Treatment VA Puget Sound – American Lake Division  Management Tacoma, Washington [email protected]

IDIOPATHIC INTRACRANIAL HYPERTENSION (IIH) – WHAT IS IT? MODIFIED DANDY CRITERIA2

 IIH otherwise known as Pseudotumor Cerebri  Diagnosis of exclusion  Causes of increased intracranial pressure (ICP) 1 Modified Dandy Criteria  Obstructive hydrocephalus, Chiari I malformation, 1. Symptoms of increased ICP various drugs, vitamin A (retinoids), venous sinus 2. No neurological signs except allowed thrombosis/stenosis, idiopathic 3. Patient is awake and alert  1 Risk factors 4. Normal CT/MRI findings without thrombosis  Obese females b/t ages of 15-40 5. LP opening pressure of >25 cmH20  Recent weight gain 6. No other explanation for increased ICP  Presenting symptoms1  Headache, pulsatile tinnitus, TVOs, , and VF constriction  Modified Dandy criteria

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USE OF OPTICAL COHERENCE DIAGNOSIS TOMOGRAPHY

 Must have imaging before lumbar puncture (LP)  CT/CT venogram, MRI/MRV (less urgent) 3  Normal opening pressure on LP: <25 cm H20  Negative imaging studies  Lack of SVP (in most patients)  Use of OCT

Lenworth, N., et al. Differentiating edema from head drusen on optical coherence tomography. Archives of . 2009. 127(1): 45-49.

TREATMENT CONTINUED –MEDICAL TREATMENT THERAPIES

 Weight loss – have shown disease resolution with  Acetazolamide (Diamox) 3 6% weight loss  CAI  Bariatric surgery  1000mg daily1,3  Discontinue known drugs that cause increased  Negative side effects ICP  Topiramate (Topamax)  Acetazolamide therapy  CAI  Topiramate therapy  Can mediate headache  Can cause weight loss  Furosemide therapy  Furosemide (Lasix)  Optic nerve sheath fenestration (ONSF)  CAI  Lumboperitoneal (LP) shunting  Ventriculoperitoneal (VP) shunting

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TREATMENT CONTINUED –SURGICAL TREATMENT CONTINUE –SURGICAL PROCEDURES PROCEDURES

 Optic Nerve Sheath Fenestration  Ventriculoperitoneal (VP) shunt  Series of slits in ONH sheath  Most successful – 30% require revision7  Procedure of choice for progressive VF loss  Must have mild HA or manageable HA

 Venous Sinus Stenting  Lumboperitoneal (LP) shunt  Very successful – 12% required revision8 5  60% required revision in trial within 5 years  Major morbidity – Subdural Hematoma

http://www.jirehdesign.com http://neuroanimations.com/Hydrocephalus/graphics/VP_Shunt_Final_lateral.jpg http://www.koraszulott.com/cikkek/Hydrocephalus http://weillcornellbrainandspine.org/sites/default/files/pseudotumor-cerebri-trial-3-lg.jpg

CASE 1 CASE 1 CONTINUED - EXAMINATION

 28 yo American Indian/Hispanic male  Rx  Presents with complaints of TVOs OD>OS  OD: -3.75-1.25x090 – no improvement in VA  h/o weight gain since discharge  OS: -4.50-0.75x079 – no improvement in VA  Strong history of mental health issues, PTSD, clinical depression, and a suicide attempt  GAT OD/OS: 17/18  DVA  Anterior segment exam unremarkable  OD: 20/30 PHNI   OS: 20/20 Posterior segment exam  Trace RAPD OD  Optic nerve: unable to determine C/D ratio d/t grade  Confrontation VF – unable to tolerate automated perimetry 4 disc edema OD and grade 3 disc edema OS  Constriction 360 with distortion/missing spots on facial amsler  Paton’s lines OU  Color plates  Macula: clear, flat, dry  OD: 3/14  Periphery: scattered white without pressure  OS: 3/14  BP: 133/82

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ODOD: OS

OS:

Modified Frisén Scale Grade II Grade I CASE 1: SPECTRALIS SD-OCT

OD:

Grade III Grade IV Grade V OS:

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DIFFERENTIAL DIAGNOSIS CASE 1 CONTINUED

 Pt very likely had increased ICP based on  MRI w/o contrast – no evidence of mass

findings/symptoms  Lumbar puncture opening pressure: 48 cm H20  Space-occupying lesion/mass in brain  CSF lab results unremarkable  Obstructive hydrocephalus  Chiari I malformation  Treatment  Drug-induced  Begin Acetazolamide 1000mg daily  Vitamin A, retinoids, indomethacin, lithium, and  Taper Depakote over next two weeks anabolic steroids  RTC 2 weeks for follow up  Venous Sinus Thrombosis/Stenosis

OD CASE 1 CONTINUED

 Did not return as scheduled  Returned two months later  Discontinued acetazolamide due to side effects few days after initiating med  On follow up:  Pt reporting constant headache/TVO’s  Trouble walking  Ran into door frame and broke a tooth  Upon observation while walking to exam room, pt was using wall as guide and refused any assistance.  Has not kept visits with neurology or neuro- ophthalmology

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Initial Visit OS

OD Two months later OS

CASE 2 CASE 2 CONTINUED - EXAMINATION

 25 yo Hispanic female  VA  OD: 20/30 PHNI  CC: PAL not working  OS: 20/20  Presents with /flashes x 3 wks, pressure  EOM testing – mild adduction deficit OD OD, light/dark adaptation issues, longstanding  FDT C-20-5 – non-specific, non-repeatable peripheral diplopia, pulsatile swishing sound x 1 year defects  h/o 60 lb weight gain over last 3 mos  No RAPD, 7mm, minimal reactivity  Denies pregnancy  Rx  OD: -3.50-0.50x175 – no improvement in VA  Strong history of mental health disease, PTSD,  OS: -2.75-1.00x175 – no improvement in VA clinical depression, and suicide attempts  Color :  h/o surgery OU before she was 3 yrs old  OD: 8/11  OS: 11/11  h/o seizures – last episode 6 mos ago  Anterior segment exam unremarkable

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OD

CASE 2 CONTINUED - EXAMINATION

 GAT OD/OS: 10/12  Posterior segment exam  Optic nerve: C/D ratio: 0.30/0.30 OU

 OD: no SVP

 OS: (+)SVP  Grade 3 disc edema OU, flame hemes around disc OU, Paton’s lines OU  Macula: clear, flat, dry  Periphery

 OD: clear

 OS: vitreoretinal tuft superiorly

OS OD OS

Initial testing

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CASE 2 CONTINUED - TESTING CASE 2 CONTINUED

 Differentials?  Poor reaction to acetazolamide – poor compliance  CT without contrast  Metallic , increased fatigue, increased  No evidence of cerebral edema depression, kidney stones  No evidence of mass  Pt has allergy to Topiramate – contraindicated  CT venogram  No improvement in disc edema, BCVA, or  No evidence of venous sinus thrombosis symptoms  Lumbar puncture opening pressure: 56 cm H 0 2  Next treatment: Optic Nerve Sheath  CSF lab results unremarkable Fenestration  OD first  Treatment  Surgical procedure performed six weeks after initial  Begin 1000mg of acetazolamide daily visit  RTC 2 weeks for follow up

OD OS

CASE 2 CONTINUED – S/P ONSF OD

 Disc edema improvement  OD: grade 1-2+ disc edema, no SVP  OS: grade 2+ disc edema, (+)SVP  VF worsening  Pt reporting unbearable headaches  No need for ONSF OS d/t intractable headaches  Next treatment: Lumboperitoneal Shunt placement  Surgical procedure performed 10 weeks after initial visit

S/P ONSF OD

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OD OS

CASE 2 CONTINUED – S/P LP SHUNT

 Pt reports nearly complete resolution of headaches  Denies TVOs  Denies pulsatile tinnitus  Disc edema improvement after ONSF OD  OD: tr disc edema, no SVP  OS: no disc edema, (+)SVP  VF improvement  Color plates: 14/14 OU  BCVA  OD: 20/25  OS: 20/15 S/P LP shunt

CASE 2 CONTINUED –REPEAT VF 1.5 CASE 2 CONTINUED YEARS LATER OD OS  Pt experienced stability in symptoms for 1.5 years  Worsening symptoms, vision, and headaches began 1.5 years after LP shunt placement  Examination  BCVA

 OD: 20/25

 OS: 20/20  Optic nerve:

 OD: no edema, mild pallor, no SVP

 OS: no edema, mild pallor, (+)SVP

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CASE 2 CONTINUED CASE 2 CONTINUED

 Next treatment:  Pt has not followed up for VF testing or Ventriculoperitoneal ophthalmologic testing since shunt placement Shunt placement  Currently undergoing inpatient health care d/t mobility issues and mental health disease  No recent VF results or ophthalmology visits

CONCLUSIONS REFERENCES 1. Subramanian, P. Idiopathic intracranial hypertension: diagnosis and management. IJSR. 2014. (4)2: 29-35  Learning objectives 2. Dandy WE. Intracranial pressure without brain tumor – diagnosis and treatment.  Definition of IIH – diagnosis of exclusion Annals of Surgery. 1937. 106(4): 492-513. 3. Wall, M. Idiopathic intracranial hypertension. Clinical Neurology 2010. 28(3): 593-  Diagnosis – modified Dandy criteria 617.  4. Lenworth, N., et al. Differentiating optic disc edema from optic nerve head drusen Pertinent testing – CT/CTV, MRI/MRV, LP, OCT, fundus on optical coherence tomography. Archives of Ophthalmology. 2009. 127(1): 45-49. photos 5. Eggenberger ER, Miller NR, Vitale S. Lumboperitoneal shunt for the treatment of pseudotumor cerebri. Neurology 1996. 46:1524–1530.  Treatment – medical vs. surgical 6. Bruce BB, Kedar S, Van Stavern GP, et al. Idiopathic intracranial hypertension in  Management – regular follow ups with VF and optic nerve men. Neurology. 2009. 72:304–309. assessment 7. Abubaker, K., et al. Idiopathic intracranial hypertension: lumboperitoneal shunts versus ventriculoperitoneal shunts – case series and literature review. British  Careful explanation to patients regarding diagnosis Journal of Neurology. 2011. 25(1): 94-99. 8. Elder, BD., et al. Venous sinus stenting is a valuable treatment for fulminant  Encourage family member to be present throughout idiopathic intracranial hypertension. Journal of Clinical Neuroscience. 2015. http://dx.doi.org/10.1016/j.jocn.2014.10.012. further testing and follow up 9. Kanagalingam, S. and Subramanian, P. Cerebral venous sinus stenting for pseduotumor cerebri – A review. Saudi Journal of Ophthalmology. 2015. 29: 3-8.  Concern of Acetazolamide worsening depressive 10. Corbett, J. et al. Visual loss in pseudotumor cerebri. Neurology. 39: 461-473. symptoms in depressed patients 11. McGirt MJ, et al. Cerebrospinal fluid shunt placement for pseudotumor cerebri- associated intractable headache: predictors of treatment response and an analysis of long-term outcomes. Journal of Neurosurgery 2004. 101(4):627–32.

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Questions? THANK YOU: ANY QUESTIONS?

 VA Puget Sound – American Lake Division  Jeffrey Hiett, O.D.  Judith Oh, O.D.

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Traumatic Brain Injury Post Trauma Vision https://dresherpt.com/concussion.asp Syndrome Diagnosis and • Caused by a bump, blow to the head, or a penetrating head injury. Management using Visual • Impact disrupts the normal function of the brain. •Estimated 1.7 million people sustain a TBI annually. Almost 5000 TBI occur daily.

Evoked Potentials (VEP) • Contributing factor to a third (30.5%) of all injury-related deaths in U.S.

Alisa Nola, O.D. • Almost half a million emergency department visits for TBI are made annually by children 0-14 years. Bright Eyes Vision Clinic • Adults aged 75 and older have highest rates of TBI-related hospitalization and death. Otsego & Minnetonka, Minnesota • In every age group, rates are higher for males than for females. [email protected] • In 2009, around 248,418 children (age 19 or younger) were treated in U.S. for sports and recreation- related injuries.

• Adverse effects of TBI include sensory, motor, perceptual, cognitive, linguistic, and attentional and/or behavioral nature.

External causes of TBI

Faul MD, Wald MM, Xu L, Coronado VG. Traumatic brain injury in the United States; emergency department visits, hospitalizations, and deaths, Faul MD, Wald MM, Xu L, Coronado VG. Traumatic brain injury in the United States; emergency department visits, hospitalizations, and deaths, 2002–2006. Centers for Disease Control and Prevention, National Center for Injury Prevention and Control, Atlanta, GA; 2010. 2002–2006. Centers for Disease Control and Prevention, National Center for Injury Prevention and Control, Atlanta, GA; 2010.

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Types of TBI Diagnosing mild TBI

• Severity • Mild: causes a brief change in mental status or consciousness. Comprises the majority of TBI (70-80%). • Cellular damages caused by mTBI is not reliably detected Concussion is the most common form of TBI. by traditional MRI testing. • Severe: causes an extended period of unconsciousness or amnesia post injury. • Functional MRI (fMRI) techniques, such as blood oxygen • Injury level dependent (BOLD) and diffusion tensor imaging (DTI) • Acceleration: the head is motionless and is struck by a have been shown to detect acute changes. more rapidly moving object. Results in a “coup” lesion. http://www.medicalclinicsofnyc.com/traumatic-brain-injury/ • Deceleration: head is moving at a rapid pace and is slowed by another external force, resulting in a • Sideline testing for saccadic dysfunction: “contrecoup” lesion. Contrecoup lesions generally affect King-Devick Testing. the brain at the injury site and directly opposite to the point of impact. • The impact of the brain crashing into the skull due to the • Vestibular and Ocular Motor Screening (VOMS) acceleration and deceleration forces (whiplash) may result in damage to the fragile brain tissue. • Neuro-optometric evaluation

• Acute and Chronic • Acute: mild TBI (mTBI) or concussion, short-term • Visual Evoked Potentials (VEP) sequelae and catastrophic brain injuries. • Chronic: neurodegenerative disorder due to repeated http://www.mayfieldclinic.com/PE-TBI.htm head trauma, includes chronic traumatic encephalopathy.

Neurological Post Trauma Vision Mechanisms Syndrome (PTVS) • Focal damage causes cortical or subcortical contusions, lacerations, and intracranial bleeding. • Post Trauma Vision Syndrome is a constellation of problems that is a result of the dysfunction between the ambient and focal visual • Mainly seen in severe cases of TBI. systems. • Diffuse injury is caused by stretching and tearing of the brain tissue. • “The majority of individuals who recover from a traumatic brain injury will have binocular function difficulties in the form of • Diffuse axonal is the main form of neuropathology , oculomotor dysfunction, convergence and of TBI and is due to acceleration and deceleration accommodative abnormalities.” (Dr. Padula and Dr. Shapiro) forces that lead to axonal shearing. • Does not require any skull fracture, direct impact, or • Disruption of the ambient visual process causes a negative impact on crush injury to the brain surface. vision and binocular dysfunction. • Mainly seen in mild cases. • Effect of vision occurs at the level of the midbrain (where vision is matched with kinesthetic, proprioceptive, and vestibular processes). • Impaired axonal transport may also lead to focal axonal swelling, followed by axonal disconnection. • is susceptible to impairment post-injury.

• Beta chemokine RANTES is elevated. • Seven out of the twelve cranial nerves and 30-40 cortical areas of the brain are involved in vision. • Widespread brain damage occur due to the initial and immediate biochemical effects and later slow-acting biomolecular and cellular mechanisms.

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Three Visual Post Trauma Vision Pathways Syndrome (PTVS)

• Parvo-cellular (80%) Signs Symptoms • Temporal/Ventral stream Diplopia • Focal Vision High Asthenopia • What?, focal, detail discrimination, Accommodative Dysfunction Poor attention & slow speed processing, and attention. Convergence Insufficiency concentration Low blink rate Headaches • Magno-cellular (18%) Spatial inaccuracy Light sensitivity • Parietal/Dorsal stream Balance and posture Perceived movement of • Ambient Vision difficulties print or stationary objects • Where?, spatial orientation, Oculomotor Dysfunction Blurred near vision posture/balance, movement, rapid Increased speed processing.

• Konio-cellular (2%) • Midbrain • Balances information between parvo and magno

PTVS Treatment

•Prisms • Low amounts of base in (BI) prism (0.5 to 1.0 prism diopters) • Yoked prisms

• Sector Patches (Binasal Occlusion)

• Lenses: Single vision glasses

• Lens Tint/Overlays https://otrobert.wordpress.com/tag/binasal-occlusion/ • Syntonics Therapy

• Neuro-optometric rehabilitation (Vision Therapy)

http://vision-therapy-pa.com/blog/b_31533_are_your_eyes_getting_flabby_do_they_need_eye_exercises.html

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Visual Evoked Potentials (VEP)

• VEPs were developed to objectively measure neurological responses of the entire visual pathway (, optic nerve, optic radiations, and ). • Visual Evoked Potential (VEP) • Photoreceptor -> bipolar -> ganglion cell axon -> relay neuron -> visual cortex neuron. • Visual –patient observes a visual stimulus • Electricity is transferred via phototransduction between each anatomical cell. • Evoked – generates electrical energy at the retina • Clinically used since at least 1970. • Potential –measure the electrical activity in the • Rapid, repeatable, and non-invasive procedure. visual cortex

International VEP VEP indications standard • Latency (ms): Indicates the time electrical signals takes to travel from • the retina to the visual cortex. Time of the P100. • • Amplitude (uV): Indicates the amount of electrical energy reaching the visual cortex. • Ischemic • N75‐P100‐N135 Complex • N75: first major negative peak that • Traumatic Brain Injury occurs around 75 milliseconds (ms). • P100: first major positive peak that occurs around 100 ms. • N135: second major negative peak that • occurs around 135 ms. • The Diopsys® NOVA‐LX uses the • Other neuropathies International VEP Standard in an advanced protocol application for an easy to use, fast VEP test that provides clear results

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P100 Latency Amplitude

Magnocellular and Stimulus Sizes Parvocellular Pathway

• Low contrast testing demonstrates degradation of magnocellular pathways • An early indication of glaucoma

• High contrast testing demonstrates degradation of parvocellular pathways • An early indicator of central vision loss and issues mostly caused by problems before signal reaches optic nerve

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Normal Vs. Abnormal vEP vEP studies in mTBI subjects

• Padula et al found improved VEP amplitudes in mTBI subjects with Binasal occlusion (BNO)

20 18 and Base-In (BI) prism.

18 16

16 14

14 12 • Ciuffreda et al also confirmed the effect of BNO on VEP in mTBI.

12 10

10 8 6 8 • Ciuffreda and Yadav optimized the VEP pattern in the visually normal and mTBI population. 4 6 2 • mTBI patients exhibited M pathway deficits and larger latency variability, thus affecting 4 Amp (µV) Amp (µV) 2 the role at low contrast levels. -2 -4 • , rather than latency appears to be a more sensitive indicator of long-term -2 Amplitude -6 -4 visual system abnormalities. -8 -6 -10 • 20min arc check size ( ) provided objective differentiation between asymptomatic and -8 64x64 -12 -10 -14 symptomatic sub-groups. 0 20 40 60 80 100 120 140 160 180 200 220 240 260 280 300 320 340 360 380 400 Time (ms) 0 20 40 60 80 100 120 140 160 180 200 220 240 260 280 300 320 340 360 380 400 Time (ms) • Ciuffreda and Yadav studied the effect of BNO and BI prism on VEP with mTBI subjects. T=15-P=64 x 64-OU-85%-C-3/25/2015 3:56:19 PM T=15-P=16 x 16-OU-85%-C-5/26/2015 11:04:43 AM T=15-P=32 x 32-OU-85%-C-3/25/2015 3:55:52 PM T=15-P=32 x 32-OU-85%-C-5/26/2015 11:05:55 AM T=15-P=16 x 16-OU-85%-C-3/25/2015 3:57:46 PM T=15-P=64 x 64-OU-85%-C-5/26/2015 11:06:26 AM • They concluded that BNO alone produced consistently larger amplitude as compared to BI prisms and with combination of BNO and BI prism in mTBI subjects. • Visually normal subjects showed decreased amplitudes with BNO and BI prism.

Mechanisms of BNO and BI TBI testing with Binasal prism occlusion

•BNO • Spread of suppression: • To decrease incoming visual motion, individuals with mTBI attempt to suppress visual motion in the peripheral VF. • Suppressive effect interacts with excitatory activity, thus reducing overall cortical excitation and VEP amplitudes. • BNO reduce the intensity of suppression, increasing VEP amps. • Faulty Filtering: individuals with mTBI manifest an inability to inhibit information from entering their stream. BNO reduces inhibition and results in a relative increase in VEP amps. • Reduces demand on peripheral fusion and help reorganize the ambient visual process.

• Base-in prism • Reduces visual stress patterns and counters spatial suppression. • Decreased vergence error by reducing convergence demand. • Optimizes the visual processing system by engaging primary visual areas (V1, V2, and V3)

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mTBI VEP Protocol

• Proposed protocol from Ciuffreda et al. • Diopsys NOVA-TR • Check size: 64x64 • Contrast: low contrast (20%) and high contrast (85%) • Luminance: 64 (cd m) • Trial duration: 20 sec • Number of trials: 3-5 trials at each stimulus condition. One outlier should be removed.

PTVS VEP Protocol Case 1

• Post Trauma Vision Syndrome Protocol • 41 y.o. CF was referred by her physician for post- • 16 and 64 Checksize: best correction OU concussion evaluation. She hit the back of her head at • 16 Checksize: 2BI OU work on 10-2-14 (7 months prior). • 16 Checksize: 2BI with BNO OU • Symptoms: dizziness, diplopia, depression, confusion, • 64 Checksize: 2BI OU light sensitivity, headache, and difficulty with reading. • 64 Checksize: 2BI with BNO OU

• Proposed Prescription Assessment • 16, 32, and 64 Checksize: best correction OU • 16, 32, and 64 Checksize: best correction and proposed prism prescription OU

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Pertinent Ocular Examination Findings: 5-13-15 (cc) OD: 20/20 Case 1 VEP OU 5-26-15 OS: 20/20 Lensometry OD: +0.25-0.50x128

OS: +1.25-1.25x129 18

16 Cover Test Distance and Near: Ortho 14

12 NPC TTN, strain, dizzy 10 8

6 Vergence ranges PFV (BO): x/18/14 4 2

(at near) NVF (BI): x/12/10 Amp (µV) -2 MEM OD: +0.75 -4 OS: +0.75 -6 -8 Binocular Crossed +0.75 OU -10 -12 Cylinder -14 0 20 40 60 80 100 120 140 160 180 200 220 240 260 280 300 320 340 360 380 400 Time (ms) PRA -1.00 OU

T=15-P=16 x 16-OU-85%-C-5/26/2015 11:04:43 AM T=15-P=32 x 32-OU-85%-C-5/26/2015 11:05:55 AM Pursuits/Saccades Smooth, dizzy T=15-P=64 x 64-OU-85%-C-5/26/2015 11:06:26 AM

T=15‐P=16 x 16‐ T=15‐P=32 x 32‐ T=15‐P=64 x 64‐ OU‐85%‐C‐5/26/2015 OU‐85%‐C‐5/26/2015 OU‐85%‐C‐5/26/2015 Stereopsis Stereopsis: RDS: 250 seconds, LDS: 5/10 11:04:43 AM 11:05:55 AM 11:06:26 AM Left Cursor Lat 49.7 ms 66.3 ms 84.8 ms Amp 3.77 uV 1.53 uV ‐0.29 uV Right Cursor Lat 81.9 ms 93.6 ms 105.3 ms Amp 17.32 uV 10.97 uV 3.91 uV Manifest OD: +0.25-0.25x130 20/20 Delta Lat 32.2 ms 27.3 ms 20.5 ms Amp 13.55 uV 9.44 uV 4.20 uV Refraction OS: +0.75-2.00x175 20/20- Eye OU OU OU Test Duration 15 sec 15 sec 15 sec Contrast 85% 85% 85% Pattern Checkerboard Checkerboard Checkerboard Ocular Health Choroidal Nevus OS CheckSize 16 x 16 32 x 32 64 x 64 Binasal N N N Correction Y Y Y SWVersion 2.15.3615 2.15.3615 2.15.3615 Filtered Y Y Y Sensor Value 138 122 99

Case 1 VEP: 2bI, BNO Case 1 VEP: 0.5BI

Amp 19.06 - Lat 102.38 18 Amp 14.91 - Lat 103.35 16 15 14 10 10 12 10 10 8 5 5 6 5 A mp 3.91 - Lat 105.30 4 Am p 3.91 - Lat 105.30

2 A m p -0.30 - Lat 85.80 Am p -0.29 - Lat 84.83 -2 -4 -5 Amp -5.37 - Lat 76.05 -5 -5 -6 -8 -10 Amp -8.81 - Lat 70.20 -10 -10 -10 -12 0 50 100 150 200 250 300 350 400 0 50 100 150 200 250 300 350 400 Time (ms) 0 50 100 150 200 250 300 350 400 T im e (m s) 0 50 100 150 200 250 300 350 400 Time (ms) Time (ms)

T=15-P=64 x 64-OU-85%-C-5/26/2015 11:12:48 AM T=15-P=64 x 64-OU-85% -C-5/26/2015 11:06:26 AM T=15-P=64 x 64-OU-85%-C-5/26/2015 11:11:11 AM T=15-P=64 x 64-OU-85%-C-5/26/2015 11:06:26 AM T=15-P=64 x 64-OU-85%-C-5/26/2015 11:09:26 AM

T=15‐P=64 x 64‐ T=15‐P=64 x 64‐ T=15‐P=64 x 64‐ OU‐85%‐C‐5/26/2015 OU‐85%‐C‐5/26/2015 OU‐85%‐C‐5/26/2015 T=15‐P=64 x 64‐OU‐85%‐ T=15‐P=64 x 64‐OU‐85%‐ 11:06:26 AM 11:12:48 AM 11:11:11 AM C‐5/26/2015 11:06:26 AM C‐5/26/2015 11:09:26 AM Left Cursor Lat 84.8 ms 76.1 ms 78.0 ms Left Cursor Lat 85.8 ms 70.2 ms Amp ‐0.29 uV ‐5.37 uV ‐3.48 uV Amp ‐0.30 uV ‐8.81 uV Right Cursor Lat 105.3 ms 102.4 ms 102.4 ms Right Cursor Lat 105.3 ms 103.4 ms Amp 3.91 uV 19.06 uV 16.16 uV Amp 3.91 uV 14.91 uV Delta Lat 20.5 ms 26.3 ms 24.4 ms Delta Lat 19.5 ms 33.2 ms Amp 4.20 uV 24.43 uV 19.64 uV Amp 4.21 uV 23.73 uV Eye OU OU OU Eye OU OU Test Duration 15 sec 15 sec 15 sec Test Duration 15 sec 15 sec Contrast 85% 85% 85% Contrast 85% 85% Pattern Checkerboard Checkerboard Checkerboard Pattern Checkerboard Checkerboard CheckSize 64 x 64 64 x 64 64 x 64 CheckSize 64 x 64 64 x 64 Binasal N N N Binasal N N Correction Y Y Y Correction Y Y SWVersion 2.15.3615 2.15.3615 2.15.3615 SWVersion 2.15.3615 2.15.3615 Filtered Y Y Y Filtered Y Y Sensor Value 99 100 132 Sensor Value 99 105 Sensor Threshold 154 154 154 Sensor Threshold 154 154 Extractor Y Y Y Extractor Y Y Operator Name Jeans,Melanie Jeans,Melanie Jeans,Melanie Operator Name Jeans,Melanie Jeans,Melanie Waveform VEP VEP VEP Waveform VEP VEP Reliability 27% 92% 83% Index Reliability 27% 78% HPrismL 2 In 2 In Index HPrismR 2 In 2 In HPrismL 5 In HPrismR 5 In With C i ht ( ) 2015 Di I BNOAll Ri ht R d 2 15 3615

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Case 1 Clinical Pearls

• Diagnosis: • Post Trauma Vision Syndrome • Imaging studies and ocular health will usually be unremarkable, but patients • Convergence Insufficiency may have many debilitating visual symptoms. • Accommodative Insufficiency • Visual Discomfort • Binasal Occlusion and Base-In prism have shown to increase VEP • Headache amplitudes. Utilizing Binasal Occlusion and Base-In prism in VEP testing • Pursuit and Saccadic Dysfunction protocol may help objectively diagnose PTVS. • Compound Hyperopic OD, OS • Choroidal Nevus OS • Treating PTVS with lenses, prisms, sector patches, and neuro-optometric rehabilitation can significantly improve the patient’s quality of life. •Plan: • 2 pairs of glasses recommended: one pair for distance tasks and one pair for near tasks. • TBIs many times result in a life-long physical, cognitive, and emotional • Distance glasses: OD: +0.25 -0.25 x130 0.5BI, OS: +0.75 -2.00 x175 0.5BI deficits that involve an emotional burden on families and a financial burden • Reading glasses: OD: +1.00 -0.25 x130 0.5BI, OS: +1.50 -2.00 x175 0.5BI on society. Managing mTBI involves a multi-disciplinary approach. • Progressive lenses and polycarbonate lenses were not recommended due to increased aberrations. Recommend CR-39 or Trivex material. • Bifocals and progressive lenses were not recommended as they may increase risk of fall and cause poor • Neuro-optometric Rehabilitation Association (NORA) is a valuable resource balance. for patients and practitioners. • Return to clinic in 1 month to assess response to prism glasses and to monitor functional visual skills. • Recommend she work on convergence, pursuits, and saccadic activities with her Occupational Therapist. • Recommend UV protection and monitoring choroidal nevus annually.

Interdisciplinary Sources Team • Blennow, Kaj, John Hardy, and Henrik Zetterberg. "The Neuropathology and Neurobiology of Traumatic Brain Injury." Neuron 76.5 (2012): 886-99.

• Ciuffreda, Kenneth J., Naveen K. Yadav, and Diana P. Ludlam. "Effect of Binasal Occlusion (BNO) on the Visual-evoked Potential (VEP) in Mild • Neuro-optometrist • Chiropractor Traumatic Brain Injury (mTBI)." Brain Injury 27.1 (2013): 41-47. • Cockerham, Glenn C., Gregory L. Goodrich, Ltc Eric D. Weichel, James C. Orcutt, Joseph F. Rizzo, Col Kraig S. Bower, and Ronald A. Schuchard. "Eye • Neurologist • Family/Caregivers and Visual Function in Traumatic Brain Injury." The Journal of Rehabilitation Research and Development 46.6 (2009): 811. • Physiatrist • Case Manager • Diopsys NOVA guide “ABCs of Electrophysiology” (4th edition). • Faul MD, Wald MM, Xu L, Coronado VG. Traumatic brain injury in the United States; emergency department visits, hospitalizations, and deaths, 2002– • Primary Care Physician • Social Worker 2006. Centers for Disease Control and Prevention, National Center for Injury Prevention and Control, Atlanta, GA; 2010.

• Hudac, Caitlin M., Srinivas Kota, James L. Nedrow, and Dennis L. Molfese. "Eye and Brain." Neural Mechanisms Underlying Neurooptometric • Rehabilitation Nurse • Sports Medicine Rehabilitation following Traumatic Brain Injury 4 (2012): 1-12.

Physician • Odom, J. Vernon, Michael Bach, Mitchell Brigell, Graham E. Holder, Daphne L. Mcculloch, Alma Patrizia Tormene, and Vaegan. "ISCEV Standard for • Neuropsychologist Clinical Visual Evoked Potentials (2009 Update)." Documenta Ophthalmologica 120.1 (2010): 111-19. • Athletic Trainer • Neuro-ophthalmologist • Padula, W. V., S. Argyris, and J. Ray. "Visual Evoked Potentials (VEP) Evaluating Treatment for Post-trauma Vision Syndrome (PTVS) in Patients with Traumatic Brain Injuries (TBI)." Brain Injury 8.2 (1994): 125-33.

• Occupational Therapist • Padula, William V., and Jannie B. Shapiro. “Head Injury and the Post Trauma Vision Syndrome.” RE:view 24.4 (1993): 153-58.

• Physical Therapist • Padula, William V. “Neuro-optoemtric Rehabilitation for Persons with a TBI or CVA.” Journal of Optometric Vision Development 23 (1992): 1-8.

• Yadav, Naveen K., and Kenneth J. Ciuffreda. "Effect of Binasal Occlusion (BNO) and Base-in Prisms on the Visual-evoked Potential (VEP) in Mild • Speech therapist Traumatic Brain Injury (mTBI)." Brain Injury Brain Inj 28.12 (2014): 1568-580.

• Yadav, Naveen K., and Kenneth J. Ciuffreda. "Optimization of the Pattern Visual Evoked Potential (VEP) in the Visually-normal and Mild Traumatic Brain Injury (mTBI) Populations." Brain Injury 27.13-14 (2013): 1631-642.

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Questions?

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Case Presentation

Ocriplasmin: • 79 yowm; new patient, diabetic eye exam • Chief complaint: • Gradual, painless decrease in vision x 3‐4 months; Boom and Bust? • Not able to isolate symptoms to one eye • POhx: • “Greying of vision” OD in 2007; patient attributes to diabetic • Noted to be throughout central and peripheral vision, stable since first Mackenzie ‘Jack’ Macintyre III O.D. noticed VA Portland Health Care System • Not sure if he woke up with these symptoms initially in 2007 Portland, Oregon • (‐)Trauma (‐)Surgeries • FOhx: unremarkable

Case Presentation Case Presentation • Clinical data (visual acuity): • Personal Medical History: (+) Polymyalgia Rheumatica • (+) Type II Diabetes Mellitus with neurological manifestations • Last A1c @ VA: 7.1 • Corrected Distance visual acuity with habitual Rx: • Hemochromatosis: occasional therapeutic phlebotomy • OD: 20/25‐1 with searching head movements • Erectile dysfunction • OS: 20/60+1 PH 20/40 • Medications: • Capsaicin 0.025% cream • Habitual Rx: • Insulin detemir • OD: +0.50 ‐0.75 x 110 • Metformin • OS: +0.75 ‐0.50 x 096 • Prednisone 5 mg • Add: +2.00 FT‐28 • Calcium carbonate • Hydrocodone/acetaminophen 500 mg • Manifest refraction Potential Acuity Pinhole: • Social History: unremarkable • OD: +0.25 ‐0.75 x 110 20/25 20/25 • OS: +0.75 ‐0.50 x 085 20/60 20/20 • Add: +2.50

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Case Presentation Case Presentation

• Clinical Data (entrance skills): • Clinical Data (anterior segment): • Pupils • Lids: MG stasis OU • 4.5/4, round, 1+ reactive (3+) APD OD • : 1‐2+ scattered fine PEE OU • 4.5/4, round, 1+ reactive • : clear OU • : Full and Comitant OU • Anterior chamber: deep & quiet OU • Cover test with habitual Rx in distance: no tropia • : Normal OU (‐)NVI OU • Confrontation Visual Field: • OD: inferior nasal and temporal and superior nasal completely • Tonometry by Goldmann applanation: 10:50 am constricted to central fixation, both with finger counting and hand motion • OD: 11 mmHg • OS: FTFC • OS: 11 mmHg

Case Presentation

• Clinical Data (posterior segment): • Lens: • OD: 1+NS; 1‐2+ ACC • OS: 2+NS; 1‐2+ ACC • Vitreous: syneresis OU; (‐)PVD OU, (‐)VH OU • Optic Disc: (‐)NVD OU • OD: 0.25/0.25, diffuse pallor • OS: 0.3/0.3, healthy rim tissue and perfusion • Maculae: (‐)CSME OU • OD: even pigmentation; • OS: mild ERM, mild central thickening? • Vessels: normal OU • Posterior Pole: (‐)Dot/Blot/Mas, (‐)HE, (‐)CWS, (‐)IRMA, (‐)VB, (‐)NVE *OU* • Periphery: No retinal holes, tears, or detachments OU

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Case Presentation

• Clinical Data (Spectralis OCT of Macula), OD:

Case Presentation Case Presentation • Clinical Data (Spectralis OCT of Macula), OS: • Assessment: • 1) Vitreomacular traction OS • 2) Vitreomacular adhesion OD; visually insignificant • 3) Optic Atrophy of unclear etiology OD • Primary Ddx: ischemic optic neuropathy, rule out compressive • 4) Type 2 diabetes with no and no clinically significant macular edema OU • 5) Mixed OS>OD • Plan: • 1‐2) Medical retina consult. • 3) Neuro‐ophthalmology consult. • 4‐5) Monitor.

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BCVA: OS: 20/60 OD: 20/25

Case Presentation The Vitreoretinal Interface • Vitreous occupies ~80% of the eye and is composed of water, collagen fibers, • Assessment: and hyaluronic acid • 1) Vitreomacular traction OS • Variably adherent to the retina • 2) Vitreomacular adhesion OD; visually insignificant • Connected to the internal limiting membrane by means of a biochemical glue: • Composed of proteoglycans (19): • 3) Optic Atrophy; most likely severe NAION • Laminin • Clear CT of head/orbits • Fibronectin • • Laminin is also found throughout the retinal layers, including: Plan: Bruch’s membrane, Ellipsoid zone (IS/OS), ELM, OPL, IPL, ILM • 1‐2) Recommend Jetrea (Ocriplasmin) injection. (1) • 3) Monitor.

• Patient received Jetrea (Ocriplasmin) injection OS in late 2014.

Journal of Ophthalmology, Volume 2012

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Pathophysiology Vitreal attachments VMA‐>VMT‐MH

• Vitreous forms several • Vitreomacular adhesion: Posterior vitreous face adhered to the macula with vitreous separation around the adhesion, without any visible deformity of the attachments to surrounding macular contour (11) structures • Strongest to weakest (19): • Vitreous base • Posterior lens • Optic disc • Macula • Retinal vessels • Other firm attachments: • Edges of retinal scars • Areas of lattice

Pathophysiology Pathophysiology VMA‐>VMT‐MH VMA‐>VMT‐MH

• Gass stage 1A/1B: Early contraction of outer part of vitreous cortex • Gass stage 2: a full‐thickness defect <400 um in width. The vitreous is with foveolar detachment (impending macular hole), and creation attached to the edges of the hole or to the cap as long as the cap is still of a foveal pseudocyst. attached to the rim of the hole (11)

• Characteristics included by other sources: vitreous is attached to the edges of the hole or to the cap as long as the cap is still attached to the rim of the hole

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Pathophysiology Pathophysiology VMA‐>VMT‐MH VMA‐>VMT‐MH

• Gass stage 3: Larger (>400 microns) central full‐thickness hole usually Gass 4: Macular hole that has an associated complete posterior vitreous accompanied by a rim of retinal elevation; the posterior cortical vitreous detachment; usually large (>400 microns) remains attached; there may be a small operculum overlying the macular hole

• Characteristics included by other sources: the posterior vitreous face is separated only over the macula

Image from www.rethinkvmt.com Image from www.rethinkvmt.com

Current Standard of Care for Diseases of the Vitreoretinal Interface From Plasmin to Microplasmin • VMA is observed after partial PVD, patients are typically asymptomatic • Plasmin: an enzyme present in blood that is involved in • As traction increases, due to both anteroposterior and tangential forces, fibrinolysis, including fibrin clots. patients can become symptomatic • Metamorphopsia, blurring of visual acuity, central visual‐field defects • 1980s: Origins in cancer research • 2002: human cadaver eyes • VMA‐VMT‐MH Stages 1‐4 • 10% of VMT will resolve spontaneously (4) • M.T. Trese and colleagues (1998‐2008): • 50% of stage 1 MH resolve spontaneously (4) • Plasmin assisted vitrectomy in repair of traumatic pediatric macular holes, • Spontaneous resolution of more advanced MH is possible but rare stage 5 retinopathy or prematurity, and complicated X‐linked ‐> successful anatomic outcomes • Vitrectomy is the current standard of care for treating more advanced • Microplasmin: recombinant, truncated form of plasmin stages of macular hole • In 2004, ThromboGenics sponsored a series of clinical trials, • Cochrane Review, Vitrectomy for macular hole: collectively called: • VA improved by 1.5 lines Microplasmin for IntraVitreous Injection • Macular hole closure with vitrectomy (76%) vs observation (11%) • Cataract surgery needed in ~50% within 2 years • rate: ~5%

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MIVI‐TRUST MIVI‐TRUST The Pivotal Study The Pivotal Study • Microplasmin for IntraVitreous Injection‐Tractional Release without • Compared a single intravitreal injection of Ocriplasmin (125 Surgical Treatment micrograms) with a placebo injection in patients with symptomatic vitreomacular adhesion • Enzymatic Vitreolysis with Ocriplasmin for Vitreomacular Traction and Macular Holes (13) • Published August 16, 2012 in The New England Journal of Medicine • Total patients = 652, all patients received an injection • *Placebo injection versus sham injection • Reported on two parallel, multicenter, randomized, double‐blind, Phase III clinical trials • Primary end point: Resolution of vitreomacular adhesion at day 28 • Funded by ThromboGenics • Secondary endpoints: • FDA approved Ocriplasmin in 10/2012 • Total PVD and nonsurgical closure of a macular hole at day 28 • Avoidance of vitrectomy • Let’s take a look…. • Change in best‐corrected visual acuity

MIVI‐TRUST: RESULTS MIVI‐TRUST Ocriplasmin Placebo P‐value Resolution of 26.5% 10.1% p=0.003 The Pivotal Study VMA; • Inclusion Criteria: Day 28 • >18 years of age Total PVD (day 13.4% 3.7% p<0.001 28) • Focal vitreomacular adhesion Non‐surgical 40.6% 10.6% p<0.001 • BCVA of 20/25 of less in the study eye and 20/800 or more in fellow eye closure of macular (according to ETDRS chart) hole • Exclusion Criteria: MH <250 um 58% • PDR, Wet‐AMD, RVO, aphakia, high myopia (>8D), uncontrolled glaucoma MH 250‐400 um 25% • A macular hole greater than 400 microns in diameter Improvement 12.3% 6.4% p=0.02 • Vitreous opacification, lenticular or zonular instability, h/o RD in VA > 3 lines, • Prior vitrectomy, PRP of the macula month 6 • Any ocular surgery, injection, or PRP in past 3 months Baseline BCVA • Presence of ERM NOT a criterion for exclusion <20/50 25.1% 11.4% >20/50 No difference No difference Vitrectomy, 6 17.7% 26.6% p=0.02 months

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SUB‐GROUP ANALYSIS Ocriplasmin Placebo MIVI‐TRUST RESULTS LENS STATUS • Summary of certain baseline characteristics that correlate with a positive clinical Pseudophakic 13.4% 3.8% outcome with intravitreal Ocriplasmin injection: Phakic 34.2% 12.6% • Age less than 65 years GENDER • Absence of Female 30.3% 13.0% • Our patient had a very minimal ERM Male 18.7% 5.5% ERM • VMA diameter of <1500 microns* • Our patient’s VMA was very focal (+)ERM 8.7% 1.5% (‐)ERM 37.4% 14.3% • Phakic lens status* Adverse event (any) 72.3% 58.5% (p=0.02) Adverse event (serious) 9.5% 10.4% (p=0.84) • * indicates presence in presented patient case 5.6% 1.6%

Update on Clinical Results: Concerns for Toxicity

• As of late 2014, a meta‐analysis of 7000+ doses based on published • Other anatomic and physiologic changes have been noted data from 14 different sites show: (23) • VMA resolution rates: 54% (range 41% ‐ 83%) after Ocriplasmin injection: • Mean VMA resolution in MH patients: 73% (range 50 ‐ 100%) • Ellipsoid zone disruption: • Mean MH closure rate: 48% (range 17% ‐ 80%) • Possibly suggesting a diffuse enzymatic effect of the protease on photoreceptors or RPE; a “loosening of the photoreceptor complex” • Another clinical characteristic that predicts improved clinical (24) outcome: • Clinical trials used TD‐OCT, not SD‐OCT • MH present (<400 microns) • Sing et al (n=17) • Successful VMT release ~ Ellipsoid zone disruption • ARVO 2015, “Extended follow‐up of Ocriplasmin for Vitreomacular Traction Release: • Average time to return of ellipsoid zone: 29.3 days • N=36 eyes • 3 posters at ARVO 2014: • 36.1% complete VMT resolution at a mean of 39.5 days • 29‐56% after 1 week, 81‐100% resolved by last follow‐up • Ocriplasmin may be used most effectively in patients with greatest linear dimension of VMT <550 microns

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Concerns for Toxicity Current Research

• Other anatomic and physiologic changes have been noted • OASIS: Ocriplasmin for Treatment of Symptomatic after Ocriplasmin injection: Vitreomacular Adhesion Including Macular Hole • Decrease in mfERG amplitudes/Dyschromatopsia • Includes ERG substudy • MIVI‐8 (completed after phase III studies) • OZONE; retrospective • N=17; 1st 4 patient c/o dyschromatopsia • Specifically looking at OCT & ERG/dyschromatopsia changes, • ERGs were obtained pre/post Ocriplasmin for other 13 patients • and INJECT Registry • 38% showed abnormal ERGs following injection, but all resolved • Clinical effectiveness and safety of Ocriplasmin • Dyschromatopsia was also shown to be transient • ERG changes and dyschromatopsia appear correlated • “First‐Line” study

• Theory: these are likely present after vitrectomy as well

Other Potential Uses For Case Update Ocriplasmin, active studies • 1 month s/p exam: • Visual acuity: 20/60‐2 (unchanged) • MIVI‐5: Ocriplasmin for Treatment of Focal Vitreomacular Adhesion in subjects with Wet‐AMD • VMT exacerbation of AMD by exterting tractional forces that stimulate neovascularization • MIVI‐II: Ocriplasmin for induction of PVD for treatment of DME • Based on observations that DME can improve with spontaneous PVD and DME is less likely in eyes with PVD • MIC: Microplasmin in Children undergoing vitrectomy not neccesarily for VMA • traumatic pediatric macular holes, stage 5 retinopathy or prematurity, and complicated X‐linked retinoschisis

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Case Update Case Update • 4month s/p exam: • 6month s/p exam: • Visual acuity: 20/50 • Visual acuity: 20/50‐2

Case Update Take home points: • 7month s/p exam: • Visual acuity: 20/60‐2 • Ocriplasmin has the potential to revolutionize how patients with pathology of the vitreoretinal interface are managed • Successful outcomes with Ocriplasmin are directly correlated with careful patient selection • Early detection of VMA/VMT/MH is key and should become more prevalent with availability of OCT technology • Vitrectomy will probably remain the treatment of choice for most eyes with MHs • Ongoing research is imperative to further investigate the safety profile of this and determine if the transient changes in retinal function (ERG/dyschromatopsia/Ellipsoid zone chnages) are due to mechanical traction release or evidence of pharmacologic toxicity.

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References References

• (1) Barak, Yoreh. "Spectral Domain Optical Coherence Tomography in the Diagnosis • (6)Garretson, BR. "Vitrectomy for a Symptomatic Lamellar Macular Hole." and Management of Vitreoretinal Interface Pathologies." Journal of Ophthalmology Ophthalmology, 2008 May; 115, no. 5, 884‐86. 2012, no. Article ID 876472. • (7) Gass JD. Reappraisal of biomicroscopic classification of stages of development of a • (2)Benz MS, Packo KH, Gonzalez V, Pakola S, Bezner D, Haller JA, Schwartz SD. A macular hole. Am J Ophthalmol. 1995; 119:752‐759. placebo‐controlled trial of microplasmin intravitreous injection to facilitate posterior vitreous detachment before vitrectomy. Ophthalmology. 2010 Apr; 117(4):791‐7. • (8) Haller JA. A single injection of ocriplasmin for the treatment of symptomatic vitreomacular adhesion (sVMA): results of the phase III MIVI‐TRUST program. Paper th • (3) de Smet MD, Gandorfer A, Stalmans P, et al. Microplasmin intravitreal presented at the Macula Society 34 Annual Meeting: March 12, 2011; Boca Raton, administration in patients with vitreomacular traction scheduled for vitrectomy: the FL. MIVI I trial. Ophthalmology. 2009;116(7):1349‐1355. • (9) Johnson MW. Posterior vitreous detachment: evolution and complications of its • (4)Ehlers, Justis P., and Pa. Philadelphia. The Wills Eye Manual: Office and Emergency early stages. Am J Ophthalmol. 2010;149(3):371‐382 Room Diagnosis and Treatment of . 5th ed. Philadelphia: Lippincott Williams & Wilkins, 2008. • (10) Kim, Judy. "Safety and Complications of Ocriplasmin." JAMA Ophthalmology 2014, 132, no. 4, 379‐80. • (5)Fahim, Abigail. Et al. "Acute Panretinal Structural and Functional Abnormalities After Intravitreous Ocriplasmin Injection." JAMA Ophthalmology 2014, 132, no. 4, • (11) Moisseiev, Joseph, Iris Moroz, and Gabriel Katz. "Effect of Ocriplasmin on the 484‐86. Management of Macular Holes." JAMA Ophthalmology 2014, 132, no. 6 (2014): 709‐ 13.

References References

• (12) Rishi, Singh. Et al. "Anatomical and Visual Outcomes following Ocriplasmin • (17) Tsui, Irena, Carolyn K. Pan, Ehsan Rahimy, and Steven D. Schwartz. "Ocriplasmin Treatment for Symptomatic Vitreomacular Traction Syndrome." British Journal or for Vitreoretinal Diseases." Journal of Biomedicine and Biotechnology 2012 (2012): 1‐ Ophthalmology 2014, no. 98, 356‐60. 6.

• (13) Stalmans, Peter, Matthew S. Benz, Arnd Gandorfer, Anselm Kampik, Aniz Girach, • (18) Witkin AJ, Ko TH, Fujimoto JG, et al.. Redefining lamellar holes and the Stephen Pakola, and Julia Haller. "Enzymatic Vitreolysis with Ocriplasmin for vitreomacular interface: an ultrahigh‐resolution optical coherence tomography study. Vitreomacular Traction and Macular Hole." The New England Journal of Medicine: Ophthalmology 2006;113:388‐97 606‐15. 2012 • (19) "Newsletters." Review of Ophthalmology® Evaluation and Management of PVD. • 14) Stalmans P, Delaey C, de Smet MD, van Dijkman E, Pakola S. Intravitreal injection Accessed September 10, 2014. of microplasmin for treatment of vitreomacular adhesion: results of a prospective, randomized, sham‐controlled phase II trial (the MIVI‐IIT trial) Retina. 2010 • (20) "Chapter 130 ‐ Vitreomacular Traction Syndrome." Free Medical Textbook. Jul;30(7):1122–1127 Accessed September 10, 2014.

• (15) Su Jeong, Song. "Ocriplasmin for Symptomatic Vitreomacular Adhesion: An • (21) Clinicaltrials.gov Evidence‐based Review of Its Potential." Core Evidence 2014, no. 9, 51‐59. • (22) Cochrane Review • (16) Tibbetts, Michael. "Vision Loss After Intravitreal Ocriplasmin." JAMA Ophthalmology 2014 132, no. 4, 487‐90. • (23) Dugel, Pravin U., Regillo, Carl D. “Ocriplasmin Clinical Update.” Healio Expert Review; 12/2014

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COPE Learning Objective

• By the end of this course, attendees will be able to recognize and describe the clinical findings associated with central retinal artery occlusion and retinal emboli, Utilizing SD-OCT as well as identify relevant retinal morphological changes in SD-OCT scans. Attendees will be able to in the Management of diagnose and manage patients presenting with these CRAO & Retinal Emboli retinal conditions.

Emily Liu, OD Optometric Resident VA Puget Sound – American Lake [email protected]

Patient Case Study Exam Findings

Personal Ocular History: • 72 year old Caucasian male • PVD OS Entering Acuities, sc OD: 20/25+, PH20/20- patient presents for his first • HST s/p laser retinopexy 2014 OS: 20/400, PHNI at this VA • Dry Eye OU Family Ocular History: EOMs Full OU • Patient thought he was due • Noncontributory Pupils RRL OU, (+)APD OS for a 6 month post-op Personal Medical History: CVF FTFC OU appointment for laser • Carotid Artery Disease retinopexy treatment of a • Hypertension Refraction OD: +0.50DS, 20/20 • h/o MI, s/p stent 2002 OS: no improvement horseshoe tear in his left eye • Dyslipidemia • Long-term smoker Anterior Segment Unremarkable OU • Chief Complaint: no initial Medications: visual or ocular complaints • 25 mg tab metoprolol tartrate Tonometry 14/16 mmHg @13:20 • 81 mg tab aspirin

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Color Fundus Exam Findings Photography Lens G1 NS, trace CS OU Vitreous (+)PVD (-)Cell OU Optic OD: 0.35R, distinct margins, (-)pallor/edema Nerves OS: 0.40R, distinct margins, (+)pallor (-)edema, (+)3 plaques overlying ONH Macula Flat, dry mottling OU Vasculatur Nicking/crossing changes OS>OD e 1 plaque, superior arcade OD 3 plaques, inferior & superior arcades OS Flame hemorrhage, superior arcade OS Peripheral OD: no H/B/T 360 Retina OS: HST s/p retinopexy, 7:00 and vitreoretinal tuft, 6:00 * Upon questioning, patient denied jaw claudication, scalp tenderness, fever or headache

SD-OCT: Optic Nerve SD-OCT: Macula

• OD: RFNL WNL 360 • OS: Severe thinning inferotemporal and superotemporal quadrants

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SD-OCT Line Scan Differential Diagnoses

Retinal Emboli Sudden Vision Loss • Calcific • Branch retinal artery occlusion • Fibrino-platelet • Central retinal artery occlusion • Cholesterol • Ophthalmic artery occlusion • Talc • Giant Cell Arteritis (AAION) • Tumor cells • Cilioretinal artery obstruction • Fat • Central retinal vein occlusion

• Retinal Detachment • or Papilledema •

Vascular Testing Results Tentative Diagnosis

Carotid Duplex • Central retinal artery occlusion with Right Highly irregular calcium multiple Hollenhorst plaques plaque observed in overlying the optic nerve and exiting proximal ICA (50-79% vasculature stenosis) and ECA (>50%) creating elevated • The patient was referred for a lipid velocities and disturbed panel, carotid duplex with vascular flow surgery consult Left Mild slightly irregular atherosclerotic plaque observed in proximal and mid ICA (16-49%) while ECA is >50% stenosed

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Laboratory Testing Results Follow Up and Treatment

Test Result Reference Blood Pressure 167/95 120/80 • Carotid endarterectomy not indicated Hemoglobin a1c 6.1 4.4 - 6.4% • Recommended regular follow-up dilated ESR 10 mm/hr 0 - 20mm/hr CRP 0.7 mg/L <=10 mg/L retinal fundus exams WBC 8.7 K/uL 4.3 - 10 K/uL • Systemic health managed by primary care RBC 4.53 Mil/uL 4.4 - 5.60 Mil/uL provider with annual carotid duplex PLT 206 K/uL 150 - 400 K/uL HGB 15.5 g/dL 13.0 - 18.0 g/dL HCT 44.8% 38.0 - 50.0% Cholesterol 257 H mg/dL 0-200 mg/dL LDL 176 H mg/dL 0 - 129

CRAO CRAO

Acute Stage (within 7 days) Chronic Stage • First described by von Graefes in 1859 • Whitened area of retina with • Optic atrophy and pallor • Incidence: ~1/100,000 corresponding visual field defect • Attenuated retinal arterial vessels • Optic nerve edema • Cilioretinal collaterals • • • Ophthalmic emergency and ocular Cherry red spot Macular RPE mottling analogue of cerebral stroke

• Unilateral acute painless severe loss of vision • Degree of vision loss dependent upon presence of cilioretinal artery

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Central Retinal Artery Occlusion CRAO: Classification

• Occurs near or at the lamina cribrosa Systemic Risk Factors • Non-arteritic permanent CRAO • Thrombosis, embolism, or • Hypertension vasculitis • Diabetes Mellitus • Most common cause of CRAO (over 2/3 of • Carotid Artery Disease cases) • Coronary Artery Disease • Embolism is the most common cause • Caused by atherosclerotic disease of CRAO • Transient Ischemic Attacks • 74% cholesterol • Cerebral Vascular • Non-arteritic transient CRAO • 10.5% calcific material Accidents • Smoking Tobacco • Non-arteritic CRAO with cilioretinal sparing • 15.5% fibrino-platelet material Ocular Risk Factors • Associated with lower incidence of macular and • 80% of complete CRAO cases have • Raised IOPs optic disc abnormalities and better visual a visual prognosis of 20/400 or worse • Optic nerve head drusen prognosis • Preretinal arterial loops • Complications: neovascularization • Arteritic CRAO secondary to Giant Cell Arteritis

CRAO: Management Retinal Emboli

• Currently no guideline-endorsed evidence of treatment • Seen in 20-30% patients upon dilated examination • Acute Treatment: restore ocular perfusion to CRA • Morphological appearance can aid • Digital massage or ocular compression with fundus contact in determining cause of CRAO lens • Poor results of inter- and intra- observer agreement on qualitative • Anterior chamber paracentesis assessment of retinal emboli • Intravenous IOP reduction • Hollenhorst (cholesterol) plaques • Hyperventilation are most common • First described in 1958 by Robert • Sub-acute Management: prevent neovascularization Hollenhorst • 75% seen clinically are • Chronic Management: prevent additional vascular events to asymptomatic occur to contralateral eye; address underlying systemic • Associated with etiology and retinal occlusions

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Vascular Diagnostic Retinal Emboli Sub-Types Testing Type Characteristic Etiology Rule out underlying Platelet- Dull-gray, elongated; tendency to Carotid disease- typically arise systemic vascular disease: Fibrin migrate from atheromas in the carotid arteries • CBC, FBS, CRP, ESR Cholesterol Sparking yellow, usually at Carotid disease - typically arise • Lipid Panel arterial bifurcation; tendency to from atheromas of carotid migrate arteries • Carotid auscultation Calcium Dull, white, typically around or on Cardiac disease - typically arise • Carotid duplex disc; typically don’t migrate form cardiac valves Cardiac Commonly in younger patients, Cardiac tumor • Transthoracic and myxoma particularly in left eye. Occlusion transesophageal often behind so no fundus (Tumor cells) echocardiography findings are seen Talc Small, yellow-white, glistening; in IV drug abuse • Computed tomographic macular arterioles angiography Lipid or Air CWS and retinal hemorrhages – Chest trauma (Purtscher’s • PT/PTT emboli are not seen retiopathy) and long bone fracture

Carotid Endarterectomy Ophthalmic Diagnostic Testing

• Surgical reduction of carotid artery Surgical Indications • Dilated Fundus Exam with Case History stenosis • Patients symptomatic for TIA or minor • Fluorescein Angiography • 26% of patients with ocular ischemia have strokes and 70-99% • Delayed retinal arterial filling no significant ipsilateral stenosis on stenosis • Prolonged arteriovenous circulation times carotid duplex • Moderate benefit for • Extensive capillary nonperfusion symptomatic patients • Circulation appears normal after 2-3 weeks • >69% of eyes with documented with 50-69% stenosis migration of emboli • Medication and risk •ERG factor modification for • Reduced B-wave amplitude • Asymptomatic Hollenhorst plaques not symptomatic patients predictive of future retinal or with <50% stenosis • B-scan Ultrasonography or Orbital CT scan cerebrovascular events • Patients with VF • Rule out compressive lesion defect associated to • Vascular testing limitations •OCT • Lack of sensitivity to detect micro- emboli

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Clinical Application of SD-OCT SD-OCT of Acute CRAO

• In vivo retinal cross sectioning with resolution up to 5 • Retinal thickening microns • Blurred margin between OPL and IPL • Evaluate subtle morphological changes within layers of retina • Thickening of INL with abnormal hyper-reflectivity • No change in ONL or GCL, but may be perceived as ‘hypo- • Ability to track patients over extended periods of time reflective’ due to back shadowing of inner retina • FA can diagnose arterial occlusions in acute stages only • Fundus autofluorescence blockage • Various imaging modes • Blockage of RPE by thickened INL • Fundus autofluorescence, red-free and infrared imaging • Limitations: hyper-reflective structures (exudates, hemorrhages, retinal vessels, etc.) result in shadowing of the underlying retinal structure • Details of such underlying morphology are lost

SD-OCT of Chronic CRAO SD-OCT of Retinal Emboli

• Inner retinal thinning • Focal hyper-reflectivity within the lumen of the blocked involving INL, GCL and blood vessel NFL • Back-shadowing of underlying structures • Normal thickness of outer retinal layers and photoreceptors

• Normal fundus autofluoresence

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SD-OCT: Infrared Photo Fundus Autofluorescence

• Noninvasive procedure utilizing fluorescence occurring naturally in the eye or accumulated as a byproduct of a disease process • Fluorophores absorb electromagnetic energy, which excites them to a higher energy stage • Triggers emission of light at Autofluorescent Ocular Materials wavelengths longer than the excitation source Calcium • Optic nerve drusen Salts • Astrocytic hamartomas • Acute CRAO shows hypo- Lipofuscin • Fundus flavimaculatus autofluorescence of non- Pigment • Best’s disease perfused retina • Resolves after 3-4 weeks

SD-OCT: FAF SD-OCT: FAF

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Conclusion References

• Aleman, Tomas S., Paul J. Tapino, and Alexander J. Brucker. "Evidence of recurrent microvascular occlusions associated with acute branch retinal artery occlusion demonstrated with spectral-domain optical coherence tomography."Retina 32.8 (2012): 1687-1688. • Noninvasive method of acute and chronic • Biller, J. O. S. É., and WILLIAM H. Thies. "When to operate in carotid artery disease." American family physician 61.2 (2000): 400-406. • Bunt, T. J. "The clinical significance of the asymptomatic Hollenhorst plaque." Journal of vascular surgery 4.6 (1986): 559-562. characterization of CRAO with OCT • Dunlap AB, Kosmorsky GS, Kashyap VS. The fate of patients with retinal artery occlusion and Hollenhorst plaque. J Vasc Surg. 2007 Dec;46(6):1125-9. • Applicable to patients with BRAO • Hayreh, Sohan Singh, and M. Bridget Zimmerman. "Fundus changes in central retinal artery occlusion." Retina 27.3 (2007): 276-289. • Hollenhorst, Robert W. "Significance of bright plaques in the retinal arterioles."Jama 178.1 (1961): 23-29. • Mathew, Raeba, Evangelia Papavasileiou, and Sobha Sivaprasad. "Autofluorescence and high-definition optical coherence tomographyof • Differentiation in etiology of retinal emboli by retinal artery occlusions." Clinical ophthalmology (Auckland, NZ) 4 (2010): 1159. • Munk, Marion R., Rukhsana G. Mirza, and Lee M. Jampol. "Imaging of a Cilioretinal Artery Embolisation." International journal of molecular comparing FAF and IR imaging with SD-OCT sciences 15.9 (2014): 15734-15740. • O'Donnell, Brett A., and Paul Mitchell. "The clinical features and associations of retinal emboli." Australian and New Zealand journal of ophthalmology 20.1 (1992): 11-17. • Puzyeyeva, Olena, et al. "High-resolution optical coherence tomography retinal imaging: a case series illustrating potential and limitations." • Evaluation of inner retinal integrity on SD-OCT as a Journal of ophthalmology 2011 (2011). • Schwarcz, Thomas H., et al. "Hollenhorst plaques: retinal manifestations and the role of carotid endarterectomy." Journal of vascular surgery marker of micro-vascular health and managing 11.5 (1990): 635-641. • Shah, Vinay A., Billi Wallace, and Nelson R. Sabates. "Spectral domain optical coherence tomography findings of acute branch retinal artery patients with ischemic risk factors occlusion from calcific embolus." Indian journal of ophthalmology 58.6 (2010): 523. • Sharma, S., et al. "Can different types of retinal emboli be reliably differentiated from one another? An inter-and intraobserver agreement study." Canadian journal of ophthalmology. Journal canadien d'ophtalmologie 33.3 (1998): 144-148. • Varma, D. D., et al. "A review of central retinal artery occlusion: clinical presentation and management." Eye 27.6 (2013): 688-697. • Varner, Paul, and Paul Varner. "The clinical import of a retinal cholesterol embolus: it is a question of symptoms." Clinical Optometry 5 (2013). • Yanoff M, Duker JS. Retinal Arterial Obstruction. Ophthalmology, 2nd ed. St. Louis: Mosby; 2004:858. • Younge, Brian R. "The significance of retinal emboli." Journal of Neuro-Ophthalmology 9.3 (1989): 190.

Questions?

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Objectives Ocular Sequelae Of • Recognize ocular sequelae Common Systemic • Identify culprit medications Medications • Properly manage

*Limitations to scope of discussion Hayley McCoy, OD VA Portland Health Care System Portland, Oregon

WHO-UMC Causality Criterion Adverse Drug Reactions (ADR) (World Health Organization-Uppsala Monitoring Centre)

Ocular Certain: • Event or laboratory test abnormality with plausible time relationship to drug intake nd • 2 most frequent organ manifesting toxicity • Cannot be explained by disease/other drugs • Tissues of different origins • Response to withdrawal plausible (dechallenge) • Event definitive pharmacologically/phenomenologically • Small mass with rich blood supply • Rechallenge satisfactory, if necessary

• High metabolic rate Probable/Likely: • Event or laboratory test abnormality, with reasonable time relationship to • Minimal impairment can have substantial functional effect drug intake • Medical specialty with fewest assessed ADRs • Unlikely to be explained by disease/other drugs • Response to withdrawal clinically reasonable • ADRs 3rd most frequent reason for malpractice suits in • Rechallenge not required Possible: ophthalmology • Event or laboratory test abnormality, with reasonable time relationship to drug intake • Could also be explained by disease/other drugs • Information on drug withdrawal may be lacking or unclear

*Unlikely/unclassified/unclassifiable categories

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Ocular side effects Common drug classes 2014 IMS health, National Prescription Audit • Dry eye • CSCR • Antihypertensives • Nervous system disorders • Hemorrhages • Optic neuritis/neuropathy • • • • /visual Mental health Anti-ulcerants disturbance • Cataracts • • Respiratory agents • Pupils/Iris • Pigment deposition • Antibacterials • Anti-ulcerants • Accommodative spasm • • Lipid regulators • Antithyroid • Eye Movement • Retinopathy

• Vascular occlusion

Most common Portland VA medications 2013-2014 Phosphodiesterase 5 (PDE5) Inhibitors Use: Erectile Dysfunction, pulmonary hypertension Drugs: Sildenafil (Viagra) Vardenafil (Levitra), Tadalafil (Cialis) 1. Sildenafil 2. Gabapentin Ocular Sequelae: 3. Tamsulosin • Dyschromatopsia • ERG changes 4. Warfarin • • AION 5. Flunisolide • Photophobia • Retinal vascular occlusion 6. Citalopram • Photopsias • Central serous 7. Cetirizine • Conjunctival hyperemia chorioretinopathy

Note: Certain side effects are rare, dose-dependent and fully reversible *Santaella & Fraunfelder: predisposing risk factors of demographic

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Phosphodiesterase 5 Inhibitors Anti-epileptics Use: Epilepsy, neuropathic pain, bipolar, insomnia, anxiety Mechanism: • Effect PDE-6 in retina Drugs: Gabapentin (Neurontin), Clonazepam (Klonopin), Diazepam • Disrupt phosphodiesterase pathway (Valium), Lorazepam (Ativan), Alprazolam (Xanax)Lamotrigine (Lamictal) : • PDE-6 mutation ~8% of RP cases Ocular Sequelae: • Dry eye • Nystagmus Management: • Blurred vision • Diplopia • Educate pt on benign nature of side effects • Photophobia • • Recommend alternative to Sildenafil • ERG/VEP changes • Use with caution in pts with: • Disrupted saccades/pursuits • History of AION • Retinitis pigmentosa or heterozygous PDE-6 defect carriers *Gabapentin: Stevens Johnson Syndrome • Refractory CSCR *Beneficial for: acquired nystagmus

Anti-epileptics Alpha 1 Adrenoreceptor Antagonists

Management: Use: Benign Prostate Hypertension, pulmonary • Pt education weigh benefit vs symptoms hypertension • Dry eye management/sun protection Drug: Tamsulosin (Flomax)

• Vitamin A helpful regenerating goblet cells Ocular Sequelae from SJS • Floppy Iris Syndrome • Consult PCP/neurologist consider reducing • Iris billows with intraocular irrigation currents dose or alternative treatment • Iris prolapse tendency • Intraoperatory pupillary constriction • Possible iris hypopigmentation

*2.3x greater chance of surgical complication

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Alpha-1 Adrenoreceptor Anticoagulants Antagonist Use: Stroke prevention, deep vein thrombosis Management: Drug: Warfarin (Jantoven/Marevan/Uniwarfin) • Thorough history and patient education Ocular Sequelae: • Ophthalmic viscoelastic device, iris hooks, malyugan ring, • Retinal hemorrhages intracameral Epinephrine injection • Subconjunctival hemorrhages • Intraoperative suprachoroidal hemorrhage Interactions: • Vitamin K • Tetracyclines/Macrolides *similar considerations with anti-platelet/aspirin

Anticoagulants Corticosteroids Use: General inflammation, asthma, COPD, MS, GCA Management: Drugs: Oral: Prednisone (Deltasone) • Patient education on effect of Vitamin K/“leafy greens” Inhaled: Flunisolide (Aerobid), Fluticasone (Flovent) • Careful medication review prior to initiation of oral IV: methylprednisolone antibiotics Ocular Sequelae: • Consider recommending INR eval with excessive or • PSC Cataracts recurrent hemorrhaging • Increased IOP/glaucoma • If pt on dual medication (ie Warfarin/Clopidogrel), • Infection Susceptibility recommended to consult PCP to d/c Clopidogrel prior to • Delayed wound healing ocular/lid procedures • • Proptosis/ • Vascular occlusion • CSCR

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Corticosteroids

Management: • Baseline comprehensive exam with VF screener • Follow up annually, sooner if indicated ie glaucoma • consider thyroid w/u for proptosis/exophthalmos • Consult with PCP /pulmonary specialist with significant adverse effects

Antidepressants Antidepressants Use: Depression, Anxiety, insomnia Drugs: Citalopram (Celexa), Amitriptyline (Evail), Trazodone Management: (Desyrel), Fluoxetine (Prozac), Paroxetine (Paxil), Sertraline • Typically eye becomes tolerant to mydriatic/cycloplegic (Zoloft effects and blurred vision resolves, otherwise topical or oral cholinergic can help Ocular Sequelae: • Education on self limiting nature of visual effects of • Blurred vision Trazodone, consult PCP regarding decreased dose or • Dry eye discontinue/alternate therapy • • Careful anterior chamber evaluation, if narrow angles • consult PCP to consider alternative such as Trazodone • Angle closure glaucoma *Selective serotonin reuptake inhibitors (SSRIs) : Increased IOP *Trazodone: palinopsia, metallic sheen, minimal activity

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H1 Antihistamine (2nd Gen): Antihistamine : Allergies Use Management: Drugs: Cetirizine (Zoloft), Loratadine (Claratin), Fexofenadine (Allegra), Promethazine (Phenergan) • Educate pt, consider severity of symptoms vs benefit of drug. • Dry eye management, education that contact lens wear Ocular Sequelae: can exacerbate • Blurred vision : will resolve rapidly when d/c • Dry eye • Radiologic imaging and neurological consultation • unnecessary since condition is drug-related. • Decreased • Oculogyric crisis

Less common Topiramate (Topamax) Anti-epilepsy

Use: Refractory epilepsy, migraines, depression, weight loss • Topiramate Ocular sequelae: Probable: • Amiodarone • Bilateral angle closure blepharospasm/oculogyric crisis glaucoma Possible: /retinal • Hydroxychloroquine • Acute myopia hemorrhage • Suprachoroidal effusion • Nystagmus* • Diplopia* • Ocular hyperemia • Uveitis

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Topiramate Amiodarone (Cordarone) Antiarrhythmic Management: Use: Atrial fibrillation, tachycardia, ventricular fibrillation • Consult with PCP to discontinue, decreasing dose as little as 50mg may have systemic adverse effects Ocular Sequelae: • ACG: Cycloplegic, corticosteroids, max IOP reducing • Optic neuropathy • Yellow/brown conj deposits therapies • B/G halos • Loss of / • Topical miotics contraindicated • Vortex keratopathy • Dry eye • PI not effective • Anterior subcapsular • B-scan may reveal choroidal effusion opacities • Blepharoconjunctivitis • Uveitis: treat with steroids rarely need to d/c • Periocular tissue • Scleritis: d/c drug for scleritis to resolve pigmentation • Maculopathy

Amiodarone Hydroxychloroquine (Plaquenil) Antimalarial/antirheumatic agent

Management: Use: Malaria, rheumatoid arthritis • Follow up q6 months for first year , then annually Ocular Sequelae: • Consultation with cardiologist/PCP to discontinue at • Maculopathy • first sign of optic nerve involvement • Vortex keratopathy • Nystagmus • Protective sunwear indicated for photophobia • Corneal edema • Ptosis • Corneal deposits • EOM paresis • Blurred vision • Photophobia • Epithelial keratopathy • Optic atrophy

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Hydroxychloroquine Management: 2011 Revised AAO recommendations: • Baseline comprehensive exam within 1 year followed by Factors Increasing the Risk of retinopathy: • Annual screening procedures after 5 years: • Duration of use >5 years • Cumulative dose >1000g • 10-2 threshold VF • FAF • Daily Dose >400mg/day or 6.5mg/kg if short • SD-OCT • mfERG • Age Elderly • NOT recommended for screening • Systemic disease Kidney or liver dysfunction • Ocular disease Retinal disease/maculopathy • Fundus Photography • Amsler grid • TD-OCT • Color Testing Rule of thumb for calculating “ideal body” weight: • Women: 100lbs + 5lbs for each inch>5ft • ffERG • EOG • Men: 110lbs + 5lbs for each inch>5ft • FA *For asthenic patients: use actual body weight • “The most important thing you can do as an optometrist is be attentive to the Consult rheumatologist to d/c with signs of toxicity patient’s dosing” - Melton and Thomas27

Additional Resources References 1. Miguel A, Henriques F, Azevedo LF, Pereira AC. Ophthalmic adverse drug reactions to systemic drugs: a systematic review. Pharmacoepidemiology and drug safety. 2014;23:221-233.

2. Fraunfelder FW. Ocular adverse drug reactions. Expert Opinion Drug Safety. 2003;2(4):411-420.

• Up-To-Date: http://www.uptodate.com/home 3. Rosenfield M, Logan N, Edwards KH. “The optometric management of ocular adverse reactions to systemic medication”. Optometry: Science, Techniques and Clinical Management. 2nd Ed. Elsevier (111-124).

• WHO-UMC: http://www.vigiaccess.org 4. Santaella RM, Fraunfelder FW. Ocular adverse effects associated with systemic medications: recognition and management. Drugs. 2007:67(1):75-93.

• National Registry of Drug-Induced Ocular Side Effects: 5. Blomquist PH, Palmer BF. Ocular complications of systemic medications. The American Journal of Medical Sciences. http://www.eyedrugregistry.com 2011;342(1):62-69. 6. Stone, K. The most common prescribed medications by drug class”. About Money. Website accessed:http://pharma.about.com/od/Sales_and_Marketing/a/The-Most-Prescribed-Medications-By-Drug-Class.htm on 06/02/15.

7. Vobig MA, Klotz T, Staak M, et al. Retinal side-effects of sildenafil. Lancet. 1999;353:375.

8. Zrenner E.: No cause for alarm over retinal side effects of sildenafil. Lancet 1999.;353:340-341.

9. Azzouni F, Abu samra K. Are phosphodiesterase type 5 inhibitors associated with vision-threatening adverse events? A critical analysis and review of the literature. J Sex Med. 2011;8:2894-2903.

10. Fraunfelder FW, Fraunfelder FT. Adverse ocular drug reactions recently identified by the national registry of drug-induced ocular side effects. Ophthalmology. 2004;111:1275-1279.

11. Cordell W, Maturi RK, Costigan TM, Marmor MF, Weleber RG, Coupland SG, Danis RP, McGettigan JW, Antoszyk AN, Klise S, Sides GD. Retinal effects of 6 months of daily use of Tadalafil or Sildenafil. Arch Ophthalmology. 2009;127(4):367-373.

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…References …References 12. Roff Hilton EJ, Hosking SL, Betts T. The effect of antiepileptic drugs on visual performance. Seizure. 21. Hasan SA. Interaction of Doxycycline and Warfarin: an enhanced anticoagulant effect. Cornea. 2007;26:742-743. 2004;13:113-128. 22. Jamula E, Anderson J, Douketis JD. Safety of continuing warfarin therapy during cataract surgery: a systematic 13. Boneva N, Brenner T, Argov Z. Gabapentin may be hazardous in myasthenia gravis. Muscle & Nerve. review and meta-analysis. 2000;23:1204-1208. 23. Clopidogrel: Herbert EN, Mokete B, Williamson TH, Laidlaw DAH. Haemorrhagic vitreoretinal complications 14. Hilton EJR, Hosking SL, Betts T. The effect of antiepileptic drugs on visual performance. Seizure. 2004;13:113- associated with combined antiplatelet agents. Br J Ophthalmology. 2005; 90(9):1209-1210. 128.

15. Noachtar S, Maydell BV, Fuhry L, Buttner U. Gabapentin and carbamazepine affect eye movements and posture 24. McCall KL, Anderson HG, Jones AD. Determination of the lack of a drug interaction between azithromycin and control differently: A placebo-controlled investigation of acute CNS side effects in healthy volunteers. Epilepsy warfarin. Pharmacotherapy. 2004;24(2):188-194. Research. 1998;31:47-57. 25. Carnahan MC, Goldstein DA. Ocular complications of topical, peri-ocular, and systemic corticosteroids. Current 16. Richa S, Yazbek JC. Ocular adverse effects of common psychotropic agents: A review. CNS Drugs. Opinion in Ophthalmology. 2000;11:478-483. 2010;24(6):501-526. 26. Oshika T. Ocular adverse effects of neuropsychiatric agents. Drug safety. 1995;12(4):256-263. 17. Liaboe L, Baker M, Oetting T. Floppy Iris Syndrome. http://webeye.ophth.uiowa.edu/eyeforum/cases/169- IFIS.htm 27. Sowka JW, Kabat AG. From migraine to angle closure: a common medication for migraine headaches can cause undesired side effects. 18. Bell CM, Hatch WV, Fischer HD, Cernat G, Paterson JM, Gruneir A, Gill SS, Bronskill SE, Anderson GM, Rochon PA. Association between tamsulosin and serious ophthalmic adverse events in older men following cataract 28. Moorthy RS, Valluri S. Ocular toxicity associated with systemic drug therapy. Current opinion in ophthalmology. surgery. JAMA. 2009;301(19):1991-1996. 1999;10:438-446.

19. Biyik I, Mercan I, Ergene O, Oto O. Ocular bleeding related to warfarin anticoagulation in patients with 29. Macaluso DC, Shults WT, Fraunfelder FT: Features of amiodarone-induced optic neuropathy. American Journal mechanical heart valve and atrial fibrillation. The journal of international medical research. 2007; 35:143-149. of Ophthalmology. 1999;127:610-612.

20. . Wells PS, Holbrook AM, Crowther NR, Hirsh J. Interactions of Warfarin with Drugs and Food. Ann Intern. 30. Mantyjarvi M, Tuppurainen KK. Ocular side effects of amiodarone. Survey of Ophthalmology. 1998;42:360-366 Med.1994;121:676-683. 31. Melton R, Thomas R. Perspectives on Plaquenil. A supplement to Review of Optometry. 2015;5(2): 12-16.

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+ + What causes a retinal artery occlusion?

 Most common cause: emboli which block blood flow to either the central retinal artery or branch of the CRA  Retinal emboli originate from various sites  Carotid artery: cholesterol (Hollenhorst) emboli  Cardiac valves: calcific emboli  Heart disease, HTN, and diabetes are common risk factors

 Other causes: Retinal Artery Occlusions  Inflammatory: including GCA, systemic lupus erythematosus, Wegener’s granulomatosis Secondary to Illicit Drug Use  Infectious: toxoplasmosis, Magi Labib, OD Lebanon VA Medical Center | Lebanon PA

+ + How about young patients? Case A

 In young patients (<40 y.), consider the following causes:  Trauma  Illicit drug abuse  57 year-old white male  Conditions leading to a hypercoagulable state  Factor V Leiden  Referred to Lebanon VA by another practitioner for  protein C and S deficiencies additional testing due to paracentral and apparent  homocystinuria positive Watzke-Allen sign  hyperhomocysteinemia  anticardiolipin antibody  cc: “blind spot” directly inferior to central vision in left eye  antiphospholipid antibody  thromboembolic disease (e.g. sickle cell disease)  Onset: about 8-9 months prior to time of exam  use of oral contraceptives  Sudden onset, stable since occurrence  renal disorders  Vascular inflammatory disorders  No other associated symptoms including eye pain, headache,  Isolated systemic hypertension etc.  Idiopathic

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+ + Case A Case A

 History of abdominal aortic aneurysm and common iliac  Early cataracts OU aneurysm s/p surgical intervention (end of 2013)

 No history of eye injuries or surgery  Recently diagnosed with HTN and hypercholesterolemia, both of which are treated; also has COPD  Family ocular history: unremarkable  Medications:  Acetaminophen  Albuterol  Amlodipine  Atorvastatin  Thiamine

 History of tobacco & drug abuse (specifically crack cocaine), and alcohol dependence  Patient admits to “heavy crack use” at exact time of onset of blind spot

+ + Case A Case A

 Visual acuity: 20/20 OU  Disc Margin: (+)perfused, sharp margins (-)pallor  Pupils: PERRL (-)APD, EOMs: full & smooth  Nerve C/D: OD .2/.2 OS .25/.25  Confrontation fields: OD: FTFC; OS: blind spot just inferior to central vision on facial amsler, periphery intact  Macula: cl ou, slightly attenuated cilioretinal artery sup. to fovea OS (not noticed until after OCT was performed) SLE: . Lids/Lash: clear  Vessels: arteriosclerosis OU (-)emboli . Sclr/Conj: pingueculae ou  Post Pole: flat/cl ou, no hemes/ischemia . Cornea: cl ou . Ant Ch: d/q ou  Periphery: flat/intact 360 OU (-)holes/tears/RD . Iris: wnl ou  Vitreous: cl OU . Angles (VH): 4 ou . Lens: NS ou

. TONOMETRY: OD: 18mmHg; OS: 18mmHg @11:00am

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+ + visual field Case A

 Primary: Old branch retinal artery occlusion

Others:  Macular hole: due to apparent Watzke-Allen sign noted at initial exam, but unlikely due to 20/20 vision  Retrobulbar optic neuritis  Ischemic optic neuropathy   Migraine with aura  Normal tension glaucoma

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+ + Case A Cilioretinal arteries: background

 Cilioretinal arteries are terminal branches of the SPCA (branch of  Diagnosis: Previous cilioretinal artery occlusion, OS ophthalmic artery)  vary in size and distribution  As confirmed by OCT/visual field  present in roughly 30% of population  Can be directly attributed to drug abuse due to timing of crack use and onset of vision loss  In the healthy eye, the presence or  Recent onset of systemic conditions (HTN, hypercholesterolemia, absence of a cilioretinal artery is aneurysms) possibly contributory clinically insignificant  Cilioretinal arteries more likely to became occluded since they  however, in the event of a retinal vascular are smaller vessels and more easily affected by vasoconstriction occlusion, the presence of a cilioretinal artery is an important factor that will determine  In this case, it was ideal that the patient’s cilioretinal artery had a smaller visual outcome distribution and occlusion led to minimal vision loss  for example, in a CRAO, the presence of a large cilioretinal artery maintains the circulation to the macular and papillomacular regions of the retina, sparing much or all of central vision

+ + Cilioretinal arteries: background Example of macular sparing in acute CRAO 8

 Systemic causes of cilioretinal artery occlusions are similar to those of a CRAO (HTN, DM, heart disease, hyperlipidemia, hypercholesterolemia, clotting disorders)  A cilioretinal artery occlusion can occur as an isolated incident (better visual prognosis), or can accompany a CRVO or ION

University of Michigan

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+ + Case A Case B 6

 First reported case of cocaine-induced CRAO associated  Work-up for an isolated cilioretinal artery occlusion is not with smoking cocaine (2002) warranted since there is typically no treatment and prognosis is good   majority of eyes return to 20/20 to 20/40 42 year-old male  GCA must be ruled out if occlusion is accompanied by ION or patient reports symptoms of GCA  Presents with sudden painless vision loss in right eye, which  If accompanied by CRVO, rule-out hypertension, heart disease, occurred 9 hours before presentation diabetes, thrombosis and hyperviscosity disorders  Management:  Normal ocular history  Communication with patient’s healthcare team regarding condition and systemic health  Medical history: sickle cell trait positive  Consider low-dose aspirin to reduce risk of recurrence  Lifestyle changes/drug counseling if related  Admitted to smoking crack cocaine twice/week for past 4 years, denied intranasal or intravenous use

Eye (2002). London.

+ 6 + Case B Right eye

 Visual acuity: OD: HM, OS: 20/15

 Pupils: (+)RAPD OD

 Ant segment: unremarkable

 Post segment:  post pole: OD: diffuse retinal whitening and edema with foveal cherry-red spot, OS: clear  vessels: vascular attenuation OD w/ segmentation of blood column; no visible emboli

 Diagnosis: Acute right central retinal artery occlusion

Eye (2002). London. Eye (2002). London.

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+ + Case B 6 Case B 6

 Immediate treatment was initiated:  6 weeks later  500 mg of acetazolamide intravenously  no change in visual acuity  intermittent ocular massage and re-breathing into a paper bag for half an hour

  Cardiovascular examination was normal with no carotid bruits or 2 months later audible murmur  visual acuity in right eye improved to 20/60  optic nerve appeared pale  Work up [to rule out other underlying factors]:  blood pressure, echocardiography, carotid Doppler, full blood count, ESR, fasting lipids and glucose: all normal  Patient was strongly advised to stop smoking, both tobacco  autoantibody screen including anti-cardiolipin antibody, protein S and C levels, and in particular cocaine antithrombin III level, Factor V Leiden, and blood homocysteine levels: also all normal

 Note: Patient was likely more susceptible to developing a CRAO from drug abuse due to his underlying sickle cell trait

Eye (2002). London. Eye (2002). London.

+ + Case C 3 Case C 3

 38 year-old female, history of IV-drug abuse  Visual acuity: OD: 20/20, OS: LP

 Admitted to the hospital after overdosing on phenytoin and  Pupils: OD: normal, diazepam OS: non-reactive to direct light, (+)consensual response

 Also was injecting large doses of cocaine intravenously  DFE:  Diffuse edematous whitening OS with foveal cherry-red spot  Immediately following recovery from overdose, she reported  No visible source of emboli loss of vision in left eye  Diagnosis: Acute left central retinal artery occlusion secondary  Ocular history: unremarkable to vasospasm from illicit drug use

Canadian Medical Association Journal 138.2 (CMAJ) Canadian Medical Association Journal 138.2 (CMAJ)

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+ + Case C 3 More on Cocaine…

 1 week F/U  Cocaine is an addictive stimulant drug obtained from the  persistent macular edema leaves of the coca plant native to South America  intravenous fluorescein angiography revealed a patent arterial system  Powdered form can either be snorted intranasally or mixed with water and injected intravenously  3 week F/U  “Crack” cocaine = smokeable form of cocaine that is  visual acuity in left eye improved to 20/120 processed with sodium bicarbonate to make a rock crystal  the crystal produces vapors that are absorbed in the bloodstream through the lungs

Canadian Medical Association Journal 138.2 (CMAJ)

+ 4 + Effects of cocaine on the body . Multiple reports of ischemic complications related to cocaine use, including:1

. myocardial infarction, stroke, intestinal  Local changes: ischemia, and abruption placentae  inhibits the re-uptake of (separation of placenta from uterine norepinephrine by adrenergic wall) nerve endings 1  causes intense . Individuals with deficiency of vasoconstriction of vascular pseudocholinesterase, the metabolizing 1 smooth muscle enzyme of cocaine, are more prone to the  leads to increased platelet serious toxic effects of cocaine, including 3 aggregation ischemia

 Systemic changes: . Other changes: tremor, insomnia, vertigo  increased vascular tone, dramatic increase in heart rate . At high doses, cocaine is extremely and blood pressure, and dangerous and can cause sudden cardiac increased myocardial arrest and death due to its inhibitory effect contraction 3 on sodium channels

7 COURSEBOOK Page 57 of 210 6/4/2015

+ + Effects of cocaine on the eye Other effects of cocaine on the eye 2

 So how do these widespread vascular changes lead to a retinal artery occlusion?  Mydriasis  Sudden widespread vasoconstriction and increased blood  Dry eye pressure causes vasospasm of the retinal arteries (central and branch), leading to occlusion of the artery and  Conjunctival injection decreased ocular perfusion  Ocular motility problems

cocaine  Acute angle closure glaucoma

 Nasolacrimal duct obstruction, , and optic neuropathy

+ + Case D 1 Case D 1

 43 year-old female  No improvement in vision with intravenous acetazolamide and  Presents with sudden painless vision loss in right eye upon globe massage waking  Brain MRI, echocardiogram, carotid Doppler, coagulation  No other complaints, initially denied any illicit drug use studies, rheumatological studies, pregnancy test, serologies for syphilis and HIV, and homocysteine assay: all unremarkable  VA: OD: NLP, OS: 20/20  A urine toxicology screen was positive for methamphetamine  Pupils: (+)APD OD  The patient then admitted to intranasal methamphetamine use 4  DFE: hours prior to waking with vision loss  OD: attenuation of vessels, foveal cherry red spot, and retinal  Also reported intranasal methamphetamine use several times a month whitening consistent with a CRAO with no prior adverse effects  no visible emboli  3 month F/U: no improvement in vision

“Central retinal artery occlusion associated with intranasal methamphetamine use” “Central retinal artery occlusion associated with intranasal methamphetamine use” (Case Report). 2003, National Stroke Association. (Case Report). 2003, National Stroke Association.

8 COURSEBOOK Page 58 of 210 6/4/2015

+ + Amphetamines 1 Visual outcome following drug- induced artery occlusions

 Amphetamines are potent stimulants used medically for the treatment of ADHD, and recreationally to attain a state of euphoria  In general, level of vision recovery usually  can be swallowed, inhaled, injected intravenously, or smoked correlates with level of entering acuity, although  Used during WWII to keep fighting soldiers going this is a generalization and there are always  Similar to cocaine, amphetamines stimulate the release of exceptions… norepinephrine and dopamine from presynaptic terminals producing elevated blood pressure, increased heart rate, and vasoconstriction  Examples of exceptions: patient from cases  Case B: HM  20/60  Amphetamines are associated with intracranial and retinal vasculitis  Case C: LP  20/120  Ischemic injury may be due to vasospasm, vasculitis, or hypertension, alone or in combination  Due to the absence of other co-morbidities, vasospasm was the likely mechanism in this patient

+ + Conclusion Questions?

 Illicit drug abuse should be considered as a possible cause of a retinal artery occlusion, especially in young, otherwise this is your eye this is you on drugs this is your eye on drugs healthy patients

 Even if illicit drug abuse is the known cause, it is still important to rule out any other compounding factors, such as hypercoagulable disorders, to prevent additional episodes or other systemic morbidities

 Consider drug testing in patients who do not admit to drug abuse and who do not have any other possible etiology

9 COURSEBOOK Page 59 of 210 6/4/2015

+ References

1. Anderson, A MD and Sung, G MD. “Central retinal artery occlusion associated with intranasal methamphetamine use” (Case Report). 2003, National Stroke Association.

2. A Y Firth. “Class A drug abuse: an ophthalmologist’s problem?”. University of Sheffield, UK. Eye (2005). 19, 609-610.

3. Devenyi, P MD, et al. “Cocaine-induced central artery occlusion.” CMAJ: Canadian Medical Association Journal 138.2 (1988): 129–130.

4. “DrugFacts: Cocaine.” NIH National Institute on Drug Abuse. Revised April 2013.

5. Friedman, N MD and Kaiser, P MD. Massachusetts Eye and Ear Infimary Illustrated Manual of Ophthalmology. 3rd Edition. 2009.

6. Michaelides, M and Larkin, G. “Cocaine-associated central retinal artery occlusion in a young man.” Eye (2002). 16, 790-792. London.

7. Quillen, D MD and Blodi, B MD. Clinical Retina. American Medical Association. 2002.

8. University of Michigan. Retina Dx. Updated 27 June 2008. http://www.kellogg.umich.edu/retinadx/retina_cases/79/photos.html.

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Objectives  Recognize retinitis pigmentosa and its associated Carbonic Anhydrase Inhibitors in conditions. Treating Retinitis Pigmentosa  Understand the pathophysiology of the condition. Associated Cystoid Macular Edema  Discuss treatment/management options of retinitis pigmentosa, particularly in cases with associated cystoid macular edema. By Victoria Roan O.D.  Discuss prognosis of visual acuity after proposed CME treatment

Jonathan M. Wainwright VAMC, Walla Walla, WA [email protected]

Bone spicule pigmentation/ pigment Symptoms / Photophobia Clinical Signs clumping Review of Retinitis Pigmentosa • Typically presenting around 20’s

 An encompassing category of several related, yet distinct, genetic Retinal arteriolar narrowing dystrophies that cause progressive loss of light-sensitive rods and cones. Tunnel vision (loss of peripheral vision)  “Retinitis” is a misnomer as inflammation only plays a small role in the • More rapidly progressive constriction Waxy pallor of the optic nerve pathophysiology. outward than toward the central field6.  1,17 • One study showed an average loss of Incidence: 1:4000; affecting about 1.5 million people 4.6% of visual field per year7. Epiretinal membrane  Primary Cases: More than 70 different modes of inheritance1,2,6,12,17: Acquired  X-linked (8-9%) • Most commonly Tritan anomaly Posterior subcapsular cataract  Autosomal recessive (16%-20%) • Initial presentation around the ages Gradual decline of acuity until 6  autosomal dominant (22%-43%) 20/40 , then fast decline. of 20-39  other (29-53%) • Large acuity range from 20/20-NLP dependent on genetic mutation and  Syndromic Cases: Over 30; best known: Usher’s Syndrome (14%)2,6,12 environmental factors. Cystoid Macular Edema • Progressive cause of visual loss, which is attributed to the loss of viable  No gender predilection; photoreceptors.  though x-linked varieties have slightly higher incidence in men1,2,6 Photopsia  Age of onset dependent on specific genetic mutation, but usually in young • Likely aberrant signals sent from degenerating retina photoreceptors adulthood. May present anywhere from infancy to mid-30’s to 50’s1,2.

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Differential Diagnosis of RP 2,6 Usher’s Disease1,5,6,29 Night-blindness in non-degenerative diseases  Autosomal recessive loss (profound or partial/ • Vitamin A deficiency • Congenital stationary night blindness congenital or late onset) & Retinitis Pigmentosa Non-evolving pigmentary  Associated with a mutation in any one of 10 genes • Rubella (salt & pepper fundus) and syphilis (“pseudo-RP”) Choroidal dystrophies  1:23,000 • Gyrate atrophy • Congenital, profound hearing loss-unable to benefit • from hearing aids Vitreoretinopathies Type 1 • Abnormal vestibular nerve function • Retinoschisis (spoke-wheel lesions at fovea) • Retinitis pigmentosa signs in early adolescents • Sarcoidosis • Mild–moderate, congenital hearing loss – benefitting from hearing aids • Type 2 • Normal vestibular response • Cone dystrophies • Retinitis pigmentosa in later adolescents Secondary pigmentary changes: • Drug toxicity retinopathy • Completely deaf and blind by adulthood • Infectious/ inflammatory retinopathy Type 3 • Will develop RP, night blindness around puberty • Traumatic retinopathy • Retinal detachment resolution

 Changes in photoreceptors: shortened outer segments- PATHOPHYSIOLOGY SUMMARY1,2,3,6,7,15,18,19 mutation of connecting cilia leading to decreased transportation of proteins (often seen in Ushers) ROD PHOTORECEPTOR  Initial reduction in numbers of rods with short or absent APOPTOSIS outer segments.

Cone photoreceptor apoptosis

RPE cell migration to inner retina

Subretinal space deterioration

Choriocapillaris atrophy A: Regular retina with long, thin rod outer segments. B: Significantly shortened and atrophied rod outer segment

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 Later stages of RP include cone death stimulated by lack of maintenance factors like interphotoreceptor retinoid-binding protein (IRBP) exclusively PATHOPHYSIOLOGY SUMMARY produced by now degenerating .  IRBP acts as a Vitamin A transport vehicle to aid in moving retinoid between retina and pigment epithelium. Rod photoreceptor apoptosis

CONE PHOTORECEPTOR APOPTOSIS

RPE cell migration to inner retina

Subretinal space deterioration

A: Normal human retina B: Human retina with RP C: RPE: retinal pigmented epithelium Choriocapillaris atrophy * : cone outer segment c : cone inner segment n : cone photoreceptor nuclei

 Cell migration from outer retina toward inner retina. • Two cell types: 1. RPE cells migrating away from the RPE layer PATHOPHYSIOLOGY SUMMARY 2. Macrophage-like cells containing melanin  Subretinal space deterioration. Rod photoreceptor apoptosis  Atrophy of choriocapillaris also often noted with onset of bone-spicule presentation.

Cone photoreceptor apoptosis

RPE CELL MIGRATION TO INNER RETINA

SUBRETINAL SPACE DETERIORATION

CHORIOCAPILLARIS ATROPHY

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 Mid-peripheral (equatorial) rods affected first, sparing 2,6,9,10,12 photoreceptors in the far periphery. Ancillary Tests  Inferior retina show earliest signs altitudinal or  Gene identification sectoral defect  ERG: a-wave: photoreceptors • H/o strong exposure to the sun or other light sources develop more b-wave: bipolar cells Normal RP severe retinal degeneration, suggesting phototoxicity. Inferior portion likely most affected from overhead light sources like sun & indoor lighting..  Visual field testing (Goldmann kinetic perimetry)  Color testing: mild blue-yellow color defects  Dark adaptation testing: increased sensitivity to bright lights  Fluorescein angiography  Ocular coherence tomography

Fluorescein Angiography vs. Ocular Coherence Tomography Current & Future Treatment/Management of RP 2,6,17:

 Genetic/Psychological counseling (eyeGENE program)  Low vision aids  Lighted magnifiers, Close-circuit televisions, Penlight, Scanning techniques  OCT has been shown to be more sensitive or at  Epiretinal/ Subretinal implants least as sensitive as FA6, 9, 10,11  i.e. - Multiple-unit Artificial Retina Chipset (MARC)  Dietary supplementation:  OCT now able to distinguish between  15,000 IU Vitamin A photoreceptor inner segment versus outer  Omega-3/ docosahexaenoic acid (DHA) supplementation—conflicting reports segment junctions8,9, 13,14.  Lutein  Retinal Transplantation  Stem Cell Therapy  Ocular gene therapy via subretinal injections.  Light/UV Protection  Hyperbaric oxygen therapy

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Meet Patient RR  71 yo WM - Initial visit to WWVAMC 2010  Systemic history: obesity, hearing loss, hypertension, hyperlipidemia, hypothyroidism.  Diagnosed with retinitis pigmentosa ~2005.  First sign of cystoid macular edema: March 2012

Hi!

Cystoid Macular Edema in RP Differential for Macular Edema

 Unclear pathophysiology, prevalence, or natural course  Diabetic retinopathy  13-38% prevalence of CME noted with OCT 9,12  Retinal vein occlusions  11-20% prevalence of CME noted with fluorescein  Uveitis angiography 12,15  Choroidal neovascular membrane  Unilateral or Bilateral  Epiretinal membranes  Chronic or Transient  Retinitis pigmentosa  Dysfunction of RPE  Increased leakage of fluid from the outer and inner blood- retinal barriers 22.  Failure of pumping mechanism 3, 4, 15, 18, 22  Vitreomacular traction 16

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Why not NSAIDS? Carbonic Anhydrase Inhibitors 6, 18,19,22, 23, 24:

 Inhibit inflammatory mediators with possible inhibition of VEGF • CAI’s occur through reversible, non-  In conditions involving leakage from vasculature, prostaglandins stimulate Arachidonic competitive binding with the carbonic inflammatory response and cause edema Acid anhdrase enzyme  NSAIDs block COX-1 and COX-2 enzymes. NSAIDs • Stimulates active transporters present along COX-1 COX-2 the RPE barrier, enhance adhesiveness of  Remember, Retinitis is a misnomer. RPE, and decrease vascular permeability. Inflammation is NOT a prominent part of pathophysiology. It is primarily Prostaglandins & • a dystrophy or genetically prostaglandins Benefits limited to disorders in which the determined degeneration of retina. Thromboxane Therefore NSAIDS do very little in RPE, rather than the retinal capillaries, resolving associated CME. appears to be major source of edema.

Let’s Compare Modes of Delivery So how did RR fair with his treatment:

 03/27/2012 - Patient was sent to Portland VAMC Retina Clinic. To p i c a l C A I : Oral CAI: OD: 20/50+2, OS: 20/25-1. He was started on topical dorzolamide BID OU. DORZOLAMIDE ACETAZOLAMIDE  05/24/2012 - Patient returned to PVAMC for f/u exam and had full resolution of CME (OD:280, OS: 279) per exam notes. OD: 20/30, OS: 20/30-1. Patient asked to PROS: PROS: continue dorzolamide BID OU. • No systemic acidosis • Higher rate of efficacy than  08/16/2012 - Follow-up exam at PVAMC revealed rebound IRF OD and possibly • 50% Efficacy dorzolamide OS (unclear notes and no OCT scan). OD: 20/30, OS: 20/25. Patient instructed to • Effective within 1-6 months. • Effective as early as 2 weeks. discontinue dorzolamide and start 250mg oral acetazolamide PO BID. • Studies have shown improvement of acuity up  10/18/2012- Two month follow-up at PVAMC to monitor for progression. to 2 snellen lines. Decreased thickness on OCT (OD: 279, OS: 273). OD: 20/30-1, OS: 20/25-1. Continue 250mg acetazolamide PO BID. CONS:  Lost to follow-up. Discontinued oral tx on his own. • 21% rebound within 6 months CONS:  10/07/2013- OD: 20/40-1, OS: 20/40-2. Persistent intraretinal fluid OD>OS • Poor compliance (OD: 276, OS: 270) Reinitiated 250mg acetazolamide PO BID. • Rare instance of efficacy • Side effects: nausea, dizziness, past 18 months. limb paraesthesia  02/11/2014- OD: 20/25+2, OS: 20/25+. Complete resolution of CME OU • Labs recommended (OD: 276, OS: 270) Discontinue acetazolamide and restart dorzolamide TID OU for prophylactic management.

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10/27/2013 02/11/2014

OD OS

 09/16/2014- Patient notes stable vision.  12/16/2014 - No subjective change in vision. Reports good compliance with oral -BCVA: OD: 20/30-, OS: 20/30+2. Reports poor compliance with topical therapy. treatment. - Rebound CME OD>OS (OD: 302, OS: 295) seen on follow-up OCT (Heidelberg). -BCVA: OD: 20/30+2, OS: 20/25-2. - Discontinue dorzolamide and restart 250mg acetazolamide PO BID. - OCT (Heidelberg): decreased macular thickness OU. (OD: 281, OS: 284) OD - Continue 250mg acetazolamide PO BID.

OD OS

OS

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 03/16/2015 - No subjective change in vision. Reports good compliance with oral treatment and no side effects of acetazolamide (i.e.- limb paresthesia, dizziness, nausea, etc) Suggested Treatment Regimen -BCVA: OD: 20/30+1, OS: 20/25-1. - OCT (Heidelberg): resolution of edema OU (OD: 283, OS: 285)

- Taper 500 mg acetazolamide PO Every Other Day. 1a 1b Persistent 1c1c1c 1gtt dorzolamide CME 6months 500mg acetazolamide Referral to Retina TID in affected QD po Specialist eye. OD OS CME resolution

222 Begin Taper CME resolution • Goal: as little dosage as possible - Order lab work- • Continue to monitor every 3-4 months for up every 3-4 months rebound.

Let’s Taper: Prognosis

 04/24/15 – OD: 20/30-1, OS: 20/30+2. Mild rebound cystoid macular edema OD>OS (OD: 294, OS: 288) Changed treatment to : 250mg Genetic mutation acetazolamide PO QD for daily control. Integrity of IS/OS and environmental  05/15/15 – OD: 20/25-2, OS: 20/30. No change OU. (OD: 297, OS: 292) junction 8,13,14 Continue acetazolamide PO QD for prophylactic management. factors 2

Acuity

Dependent on duration / stage of Extent of CME 9 RP

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1. Milam, Ann H., Zong-Yi Li, and Robert N. Fariss. "Histopathology of the Human Retina in Retinitis Pigmentosa." Progress in Retinal and Eye Research 17.2 (1998): 175-205. Print.

2. Hamel, Christisan. "Review: Retinitis Pigmentosa." Orphanet Journal of Rare Diseases , vol 1,no1, article no 40, ((2006).

3. Rodrigues, Merlyn M., Barbara Wiggert, Joseph Hackett, Ling Lee, R. Theodore Fletcher, and Gerald J. Chader. "Dominantly Inherited Retinitis Pigmentosa." Ophthalmology: 1165-172. Print.

Key Points: 4. Chader GJ, Wiggert B, Lai YL, et al. Interphotoreceptor retinoid-binding protein: a possible role in retinoid transport to the retina. Prog Retinal Res 1983; 2:163-89.

5. Fahim AT, Daiger SP, Weleber RG. Retinitis Pigmentosa Overview. 2000 Aug 4 [Updated 2013 Mar 21]. In: Pagon RA, Adam MP, Ardinger HH, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2015.Shintani, Kelly, Diana L. Shechtman, and Andrew S. Gurwood. "Review and Update: Current Treatment Trends for Patients with Retinitis Pigmentosa." Optometry - Journal of the American Optometric Association 80.7 (2009): 384-401. 1. RP is not primarily an inflammatory condition and should 6. Berson El, Sandberg MA, Rosner B, et al. Natural course of RP over a 3-yr interval. Am J Ophthalmol 1985;99:240-51. 1. 7. Sandberg MA, Brockhurst RJ, Gaudio AL, et al. The association between VA and central thickenss in RP. Invest Ophthalmol Vis Sci 1980;46:3349-54. not be treated as such. 8. Hirakawa, H, Iijima H, Gohdo T, Tsukahara S. Optical Coherence tomography of cystoid macular edema associated with retinitis pigmentosa. AM J Ophthalmol 1999; 128:185-91. 9. Apushkin, Marsha A., Gerald A. Fishman, and Mark J. Janowicz. "Monitoring Cystoid Macular Edema by Optical Coherence Tomography in Patients with Retinitis Pigmentosa." Ophthalmology 111.10 (2004): 1899-904. Web. - CAI’s have shown to be effective in treating CME 10. Hee MR, Puliafito CA, Wong C, et al. Quantitative assessment of macular edema with optical coherence tomography. Arch Ophthalmol 1995;113:1019-1029 11. Hajali, M., and G. A. Fishman. "The Prevalence of Cystoid Macular Oedema on Optical Coherence Tomography in Retinitis Pigmentosa Patients without Cystic Changes on Fundus Examination." Eye 23.4 (2008): 915-19. Web. associated with RP 12. Oishi, A., A. Otani, M. Sasahara, H. Kojima, H. Nakamura, M. Kurimoto, and N. Yoshimura. "Photoreceptor Integrity and Visual Acuity in Cystoid Macular Oedema Associated with Retinitis Pigmentosa." Eye 23.6 (2008): 1411-416. 13. Oishi A, Nakamura H, Tatsumi I, Sasahara M, Kojima H, Kurimoto M et al. Optical coherence tomographic pattern and focal electroretinogram in patients with retinitis pigmentosa. Eye. 2008. in press. - Start topical dorzolamide TIDoral acetazolamide 14. Heckenlively, John R, Berry L Jordan, and Nata Aptsiauri. "Association of Antiretinal Antibodies and Cystoid Macular Edema in Patients with Retinitis Pigmentosa." American Journal of Ophthalmology: 565-73. Print. 15. Takezawa M, Tetsuka S, Kakehashi A. Tangential vitreous traction: a possible mechanism of development of cystoid macular edema in retinitis pigmentosa. Clin Ophthalmol. 2011; 5: 245–248.

16. Musarella, Maria A., and Ian M. Macdonald. "Current Concepts in the Treatment of Retinitis Pigmentosa." Journal of Ophthalmology 2011 (2011): 1-8.

500mg /day 17. Thobani, Azzrah, and Gerald A. Fishman. "The Use Of Carbonic Anhydrase Inhibitors In The Retreatment Of Cystic Macular Lesions In Retinitis Pigmentosa And X-Linked Retinoschisis." Retina 31.2 (2011): 312-15

18. Wolfensberger TJ, The Role of carbonic Anhydrase Inhibitors in the management of macular edema. Doc Ophthalmol. 1999; 97:387-397. [PubMed:10896355] 2.2. Since RP encompasses a large variety of genetic mutations, 19. Chen, JC, Fitzke FW, Bird AC. Long-term effect of acetazolamide in a patient with retinitis pigmentosa. Invest Ophthalmol Vis Sci 1990; 31:1914-8. 20. Fishman GA, Gilbert LD, et al. Acetazolamide for treatment of chronic macular edema in retinitis pigmentosa Arch Ophthalmol 1989; 107: 1445-52.

each case will need to be specifically tailored to the patients’ 21. Cox SN, Hay E, Bird AC Treatment of chronic macular edema with acetazolamide (1988) Archives Ophthalmology 106:1190-1195marmo

22. Marmor MF, Negi A. Pharmacologic modification of subretinal fluid absorption in the rabbit eye. Arch Ophthalmol 1986; 104:1674-7. circumstances. 23. Moldow B, Sander B, Larsen M et al. (1996) The effect of acetazolamide on leakage and outward active transport of fluorescein across the blood-retinal barrier in healthy subjects. Invest Ophthalmol Vis Sci 37:S106 24. Kawasaki, Kazuo, Shigeo Mukoh, Daizo Yonemura, Shigeru Fujii, and Yasunori Segawa. "Acetazolamide-induced Changes of the Membrane Potentials of the Retinal Pigment Epithelial Cell." Documenta Ophthalmologica 63.4 (1986) 3. Lastly, vision loss is a natural progression of this condition. 25. Grover, Sandeep, Marsha A. Apushkin, and Gerald A. Fishman. "Topical Dorzolamide for the Treatment of Cystoid Macular Edema in Patients With Retinitis Pigmentosa." American Journal of Ophthalmology 141.5 (2006): 850-58. 3. 26. Apushkin, Marsha A., Gerald A. Fishman, Sandeep Grover, and Mark J. Janowicz. "Rebound Of Cystoid Macular Edema With Continued Use Of Acetazolamide In Patients With Retinitis Pigmentosa." Retina 27.8 (2007): 1112-118. Decrease in acuity with or without macular edema is 27. Orzalesi, Nicola, Chiara Pierrottet, Alessandro Porta, and Monica Aschero. "Long-term Treatment of Retinitis Pigmentosa with Acetazolamide." Graefe's Archive for Clinical and Experimental Ophthalmology 231.5 (1993): 254-56. 28. Genead MA, Fishman GA. Efficacy of sustained topical dorzolamide therapy for cystic macular lesions in patients with retinitis pigmentosa and Usher syndrome. Arch Ophthalmol. 2010; 128(9):1146-1150.

29. Ikeda, Y., N. Yoshida, S. Notomi, Y. Murakami, T. Hisatomi, H. Enaida, and T. Ishibashi. "Therapeutic Effect of Prolonged Treatment with Topical Dorzolamide for Cystoid Macular Oedema in Patients with Retinitis Pigmentosa." British expected. Though treatment of CME may be successful, acuity Journal of Ophthalmology 97.9 (2013): 1187-191

30. Fishman, G. A., and M. A. Apushkin. "Continued Use of Dorzolamide for the Treatment of Cystoid Macular Oedema in Patients with Retinitis Pigmentosa." British Journal of Ophthalmology 91.6 (2007): 743-45.

is not always going to improve. 31. Grover, Sandeep, Gerald A. Fishman, Richard G. Fiscella, and Adrienne E. Adelman. "Efficacy Of Dorzolamide Hydrochloride In The Management Of Chronic Cystoid Macular Edema In Patients With Retinitis Pigmentosa." Retina 17.3 (1997): 222-31.

32. Grover, Sandeep, Gerald A. Fishman, Richard G. Fiscella, and Adrienne E. Adelman. "Efficacy Of Dorzolamide Hydrochloride In The Management Of Chronic Cystoid Macular Edema In Patients With Retinitis Pigmentosa." Retina 17.3 (1997): 222-31. Web.

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Financial Disclosure

 Remember I am a Resident, Current Trends  Therefore NO financial interest in any and Future company or product mentioned. Advances in Cataract Surgery.

Kolten R. Kuntz, O.D.

Cataract Surgery Today Cataract Surgical History  20.5 million Americans  An increase in  ICCE - 1864 with cataracts. baby boomers  Intra-capsular  22 million procedures desiring high  ECCE -1865 worldwide per year quality refractive  Extra-capsular  3 million in America outcomes.  1948-1980’s  95-98% overall success  Desire an earlier  MSICS rate in the US  CDC 2013 treatment before  Small incision ECCE  99.5% with no severe significant visual  Phacoemulsification post-op Complications reduction.  1967  CDC 2013   Capsulorhexis with  An Increased demand Post-op success Phacoemulification for the latest =+/-0.50D instrumentation and  Intra-Ocular Lens  57% within +/-0.5D refractive outcome.  FDA approved in 1981

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Pre-Operative Measurements Intra-ocular Lenses  Spherical IOL- 1948  Future of the IOL?  Immersion A-Scan  Holladay 2  FDA1981  Electronic/Auto-  Manual Biometry  Aspehric IOL- 2004  SRK/T focal IOL  Manual K’s  Toric IOL  ELENZA  Manual Calcs  Multifocal IOL  2018  Now all in-one  Multi-focal Toric IOL  Biometry  AcrSof Restor  Keratometry  Abbott Technis  Pachymetry  Crystalens  Pupilometry  Trulign Toric  Lens Calcs  IOLMASTER 500  LENSTAR LS 900

Premium Refractive IOL Extended Range IOLs

 AcrySof ReSTOR IQ  Technis Multifocal  Crystalens  Trulign Toric  ReSTOR Toric  independent  Apodized full diffractive diffractive Optic posterior surface

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Intra-operative Refractive Diagnostics

 Verion Image  ORA System Guided System  Real-time  d  Blueprint for intraoperative corneal incision refractive and IOL alignment. measurements.  23% residual cylinder to10% in Toric IOL implants

 d

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Femtosecond Laser Assisted Cataract Surgery FLACS

 Approved for LASIK  FDA approved for: Surgery since 2001  Corneal incisions  Approved for  Nuclear Cataract Surgery in fragmentation the US since 2010  Capsulorhexis (Dr. Steven Slade)  Limbal Relaxing Incisions

Femtosecond Laser Platforms

Abbott Catalys LensAR Alcon LenSX B+L Victus

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Real Time OCT Imaging Clear Corneal Incisions CCI

Anterior Capsulotomy Phacofragmentation

 Allows for a 43% reduction in phaco power/ energy  51% reduction in phaco time  Theoretically resulting in a safer surgery with a more predictable outcome.

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Limbal Relaxing Incisions (LRI) Laser Arcuate Incisions

d  d  d

Complicated Cases  Fuchs Endothelial Dystrophy  Reducing endothelial cell disruption and loss  Hypermature White Cataracts  Have greater risk of incomplete capsulorhexis, posterior capsule rupture, endothelial cell loss and incision complications

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Intra-opertive advances

 Better Viscoelastic  Future attempts to Solution eliminate the use  Improved diamond blades of ultrasound in the  Real-time OCT eye and  Abberometry and dramatically ORA measurements reduce incision  Polishing tips size. Thank You.  Polishing the https://www.youtube.com/watch?feature=player_detailpage&v=xO posterior capsule Pp__u3Soc while removing the cortex of the lens.  Better BSS saline

References

 Nagy Z, Takacs A, Filkorn T, Sarayba M. Initial clinical evaluation of an intraocular femtosecond laser in cataract surgery. J Refract Surg 2009;25:1053-60.  Palanker DV, Blumenkranz MS, Andersen D, et al. Femtosecond laser-assisted cataract surgery with integrated optical coherence tomography. Sci Transl Med 2010;2:58ra85.  Masket S, Sarayba M, Ignacio T, Fram N. Femtosecond laser-assisted cataract incisions: architectural stability and reproducibility. J Cataract Refract Surg 2010 Jun;36(6):1048-9  Miháltz K, Knorz MC, Alió JL et al. Internal aberrations and optical quality after femtosecond laser anterior capsulotomy in cataract surgery. J Refract Surg. 2011;27:711-6  Friedman NJ, Palanker DV, Schuele G et al .Femtosecond laser capsulotomy.J Cataract Refract Surg. 2011;37:1189-98.  Kránitz K, Miháltz K, Sándor GL et al Intraocular Lens Tilt and Decentration Measured By Scheimpflug Camera Following Manual or Femtosecond Laser-created Continuous Circular Capsulotomy. J Refract Surg. 2012;28:259-63.  Ratkay-Traub I, Juhasz T, Horvath C, et al. Ultra-short pulse (femtosecond) laser surgery: initial use in LASIK flap creation. Ophthalmol Clin North Am 2001;14:347-55.  Kim P, Sutton GL, Rootman DS. Applications of the femtosecond laser in corneal refractive surgery. Curr Opin Ophthalmol 2011;22:238-44.  Sutton G, Hodge C. Accuracy and precision of LASIK flap thickness using the IntraLase femtosecond laser in 1000 consecutive cases. J Refract Surg 2008;24:802-6.  Kezirian GM, Stonecipher KG. Comparison of the IntraLase femtosecond laser and mechanical keratomes for laser in situ keratomileusis. J Cataract Refract Surg 2004;30:804-11.  Images: Google Images

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The Importance of Optical Centration in Multifocal Soft Contact Lenses Financial Disclosure

The Effects of Decentering Multifocal Soft Contact Lens Optics and its Relation to Distance Vision SpecialEyes Inc. is currently providing funding and contact lenses for our research in optical centration in multifocal contact lenses.

Frank Zheng, OD Pacific University College of Optometry 2015 Residency Conference

Multifocal Soft Contact Lenses Optical Alignment is Crucial

Concentric Distance Aspheric Distance Aspheric Near Center Center Center Concentric Distance Aspheric Distance Aspheric Near Center Center Center Distance Distance Distance Distance Distance Distance

Near Near Near Near Near Near

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Concentric Distance Aspheric Distance Aspheric Near Center Center Center Multifocal Soft Contact Lenses

1. Ocular Anatomy ◦ Right Eye vs. Left Eye 14.00mm14.00mm 14.00mm

8.0mm 8.0mm 8.0mm 2. Pupil Size and Location ◦ Superior Nasal Decentration of Pupils

3. Location of the Visual Axis ◦ Compensating for Angle Kappa

2.0mm 2.0mm 2.0mm

Soft Lens Centration Based on Multifocal Centration Scleral Measurement Walker, M. et al. 2013 1. Surface Anatomy RL

Nose

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SCL Lens Position Study N = 18 Subjects 18 17 17 16 15 15 14 13 12 11

Subjects 10 Angle

of 9 8 7 6

Number 5 4 3 3 2 1 1 0 Right Eyes Left Eyes Temporal Centered

Medial Rectus Insertion

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Pupil 4.0 mm 2.0 mm CL Optic Temporally Displaced Right Lens

Line of Sight

+

CL Distance Optic

Multifocal Centration Pupils Are Displaced Nasally

2. Pupil Size & Location

Temp Nasal

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Pupil Position Within the Iris: An Right Eye Internal Perspective Walker, M. et al. (2013) Right Eye

Right Eye

T N

Left Eye

Left Eye Multifocal Centration

3. Visual Axis

Left Eye

N T

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Where is our Fovea?! Center of the Cornea ≠ Visual Axis

Optical Centration in Refractive Surgery Study Subjects Context Outcome Refractive Surgery Wachler et al. N=1 Lasik corneal ablation: pupillary axis VS. Significantly better visual outcome when optics corneal light reflex centered over the corneal light reflex

Chat et al. N=21 LASIK centered over the corneal light reflex Significantly better visual outcome when optics instead of the pupillary axis in hyperopic eyes centered over the corneal light reflex

Arbelaez et. Al N=53 Compared ablation zone between corneal Less induced ocular aberrations and asphericity when vertex and pupil centered angle kappa was accounted for

Khakshoor et al. N=348 Compared small (less than 5 degrees) vs large Utilizing corneal light reflex as ablation center: better angle kappa values pre‐LASIK refractive outcomes, especially with large angle kappa Kermani et al. N=170 Retrospective review of post LASIK patients: Significant reduction in induced coma aberration in ablation centered on corneal light reflex vs those who had ablation centers closer to the corneal pupillary axis light reflex

Prakash et al. N= 76 Retrospective review on dissatisfied patients Patients who had complaints about glare and halo with multifocal IOL and their pre‐surgical angle showed a positive correlation with pre‐operative kappa values angle kappa values.

Park et al. NA Large literature review on angle kappa and its Compensating for angle kappa in refractive surgery, (2012) relevance in refractive surgery especially in hyperopes is of significant importance Moshirfar et al. for visual prognosis (2013)

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8.00mm N Where Should We Center the Lens? T

Conventionally ◦ Center the lens over the cornea

2.00mm

T N Corneal Topography Display Axial Display Tangential Display 0.50mm 0.50mm

Visual Axis

1.00mm

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Multifocal Contact Lenses Temporally Off‐Centered Lenses R L

X X

Eye clarity 4/10 Eye clarity 2/10 Eye fluctuation 6/10 Eye fluctuation 6/10 Eye ghosting 6/10 Eye ghosting 6/10 Visual Acuity 20/30 Visual Acuity 20/40‐1

Temporally Off‐Centered Lenses Temporally Off‐Centered Lenses R L R L

X X X X

Eye clarity 4/10 Eye clarity 2/10 Eye clarity 4/10 Eye clarity 2/10 Eye fluctuation 6/10 Eye fluctuation 6/10 Eye fluctuation 6/10 Eye fluctuation 6/10 Eye ghosting 6/10 Eye ghosting 6/10 Eye ghosting 6/10 Eye ghosting 6/10 Visual Acuity 20/30 Visual Acuity 20/40‐1 Visual Acuity 20/30 Visual Acuity 20/40‐1

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Multifocal Contact Lenses Optimized Centered Contacts R L

X X

Eye clarity 8/10 Eye clarity 8/10 Eye fluctuation 9/10 Eye fluctuation 10/10 Eye ghosting 8/10 Eye ghosting 9/10 Visual Acuity 20/20‐1 Visual Acuity 20/20‐1

Optimized Centered Contacts Optimized Centered Contacts L RL RR L

X X X X

X X

Eye clarity 8/10 Eye clarity 8/10 Eye clarity 8/10 Eye clarity 8/10 Eye fluctuation 9/10 Eye fluctuation 10/10 Eye fluctuation 9/10 Eye fluctuation 10/10 Eye ghosting 8/10 Eye ghosting 9/10 Eye ghosting 8/10 Eye ghosting 9/10 Visual Acuity 20/20‐1 Visual Acuity 20/20‐1 Visual Acuity 20/20‐1 Visual Acuity 20/20‐1

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Implications References 1. Studebaker J. et al “Soft Multifocals: Practice Growth Opportunity.” Contact Lens Spectrum; June 2009. Available at: www.clspectrum.com/article.aspx?article=103013; last accessed Nov. 28, 2011)

2. Dzurinko, V. et al “Today’s Multifocal Opportunity.” Contact Lens Spectrum; Feb 2012. Available at: Myopia Control www.clspectrum.com/articleviewer.aspx?articleID=106665; last accessed Apr. 4, 2015)

◦ Improved distance vision with high ADD multifocal contact Lenses 3. Sheedy, James E., Harris G. Michael, Busby Leslie, Chan, Eileen, and Koga, Irene. “Monovision Contact Lens Wear and ◦ Reduced aberrations associated with multifocal contact lenses Occupational Task Performance” American Journal of Optometry & Physiological Optics Vol. 65, No. 1 pp 14‐18 4. Ardaya D., Devuono G, Lin I, Neutgens A, Bergenske P, Caroline P, Smythe J. “The Effect of Add Power on Distance Vision with the Acuvue Bifocal Contact Lens.” Optometry 2004 Mar: 75(3): 169‐74

5. http://pabloartal.blogspot.com/2008/08/on‐definition‐of‐angle‐kappa.html ; Web Accessed 4/12/2015 6. Wachler BS, Korn TS, Chandra NS, Michel FK. “Decentration of the optical zone: centering on the pupil versus the coaxially ◦ Projected to be the largest population of contact lens wearer by 2018 sighted corneal light reflex in LASIK for hyperopia.” J Refract Surg 2003; 19:464–465. 1‐2 ◦ (28% of all contact lens wearers ~ 13.5 million people) 7. Chan CC, Boxer Wachler BS. “Centration Analysis of Ablation over the Coaxial Corneal Light Reflex for Hyperopic Lasik” J Refract ◦ Increase success rate with multifocal contact lenses Surgery 2006; 22:467‐471 8. Arbelaez MC, Vidal C, Arba‐Mosquera S. “Clinical outcomes of corneal vertex versus central pupil references with aberration‐ free ablation strategies and LASIK.” Invest Ophthalmol Vis Sci 2008; 49:5287–5294.

9.Hamid Khakshoor, Michael V McCaughey, Amir Hossein Vejdani, Ramin Daneshvar, and Majid Moshirfar. “Use of angle kappa in myopic photorefractive keratectomy” Clinical Opthalmology Jan 2015 Vol 9 Web. Accessed:4/12/2015

References References 10. Kermani O, Oberheide U, Schmiedt K, et al. Outcomes of hyperopic LASIK with the NIDEK NAVEX platform centered on the 19. Sheedy, James E., Harris G. Michael, Bronge R Matthew, Joe M. Sharon, and Mook A. Melanie, “Taskand Visual visual axis or line of sight. J Refract Surg 2009; 25 (1 Suppl.):S98–S103. Performance with Concentric Bifocal Contact Lenses” Optometry and Vision Science 1991 Vol 68, No. 7 pp. 537‐541

11. Prakash G, Agarwal A, Prakash DR, et al. Role of angle kappa in patient dissatisfaction with refractive‐design multifocal intraocular lenses. J Cataract Refract Surg 2011; 37:1739–1740.

12. Prakash G, Prakash DR, Agarwal A, et al. Predictive factor and kappa angle analysis for visual satisfactions in patients with multifocal IOL implantation.Eye (Lond) 2011; 25:1187–1193

13. Park, Choul Yong, Sei Yeul Oh, and Roy S. Chuck. "Measurement of Angle Kappa and Centration in Refractive Surgery." Current Opinion in Ophthalmology 23.4(2012): 269‐75. Web. 5 Apr. 2015

14. Moshirfar, Majid, Ryann Hoggan, and Valliammai Muthappan. "Angle Kappa and Its Importance in Refractive Surgery." Oman Journal of Ophthalmology 6.3 (2013): 151. Web.

15. Moshirfar, Majid and McCaughey, Michael “The Relevance of Angle Kappa in Refractive Surgery” Contaract & Refractive Surgery Today Sept 2014,. Web. 5 Apr 2015

16. Van Der Worp, E. Schweizer, H. Lampa, M., Van Beusekom, M. and Andre M. “The Future of Soft Contact Lens Fitting Starts Here” Contact Lens Spectrum Jun 2014. Web 5 April 2015

17. Gatinel, Damien “Centering Corneal Based Refractive Surgery” http://www.gatinel.com/recherche‐formation/centering‐ corneal‐based‐refractive‐surgery/

18. Jackson, Mitchell MD “Hidden Threats to IOL Satisfaction: Beware the effects of spherical aberration and angle kappa on IOL selection” Ophthalmology Management, Volume: 16 , Issue: July 2012, page(s): 33 ‐ 35

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Image Sources 1. http://visitforestgrove.com/about‐forest‐grove/pacific‐university/ 2. http://briancartergroup.com/social‐media‐roi/the‐5‐biggest‐facebook‐ad‐mistakes/?hvid=2f7iuh 3. https://www.alohalaservision.com/wp‐content/uploads/2011/01/shutterstock_27257383.jpg 4. http://city‐sentinel.com/2013/01/baby‐boomers‐have‐options‐regarding‐social‐security/ 5. http://www.weightoffmyshoulders.com/blog/2014/02/three‐things‐thursday‐5 5. http://ezhowtotips.com/how‐to‐know‐if‐your‐child‐needs‐glasses 6. http://roseoptom.co.nz/index.php/for‐your‐eyes/specialty‐services/myopia‐control/ 7. http://www.allaboutvision.com/parents/myopia.htm 8.http://contactlenseschoosing.com/bifocal‐contact‐lenses/ 9. http://www.clspectrum.com/articleviewer.aspx?articleID=111205 10. http://www.ophthalmologymanagement.com/articleviewer.aspx?articleID=107209 11. http://www.hawal‐eg.com 12. http://www.gatinel.com/recherche‐formation/centering‐corneal‐based‐refractive‐surgery/ 13. https://www.pinterest.com/bonnietjie/cats‐with‐glasses/

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Disclosure

 The content and format of this course is presented without commercial bias and does not claim superiority of any commercial product or service.

Differential Diagnoses of Post‐Operative Uveitis Warren Whitley, OD Optometry Resident Eye Care Associates of Nevada

Learning Objectives

 To identify the differential diagnoses of uveitis

 To review treatment options of uveitis

 To apply knowledge to clinical use

Review of Uveitis, Causes and Treatment

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Anatomy and Physiology Uveitis

 Affects 15 per 100,000 in the U.S. population (38,000 cases/year)

  Uveal Tract Mean age of onset is ~40 years.  5‐10% of these cases occur in children under age 16  Iris‐ anterior extension of  Ciliary body – posterior extension of iris  Third leading cause of preventable blindness in developed countries  – Accommodation  10‐15% of all blindness in the United States  2 Layers of epithelium  Outer –RPE  Causes:  Inner –sensory retina, produces aqueous  50% ‐ idiopathic conditions  Choroid – supplies nutrition for external retina  20% ‐ trauma  20% ‐ underlying systemic condition  Function is nourishment, gas exchange, and light absorption  10% ‐ localized ocular condition (e.g. herpes zoster, toxoplasmosis)

Retrieved from http://www.uveitis.org/patient/glossary/t‐z#UVEITIS

Examination Signs/Symptoms

 Symptoms  Begins with a thorough case history  Pain  Redness  Structures involved:  Photophobia  Anterior uveitis (anterior chamber)  Consensual photophobia  (ciliary body and vitreous)  Decreased vision  Posterior uveitis (retina and choroid)  Epiphora  Panuveitis  Signs  Acute vs. chronic  Cells and flare in the anterior chamber  Ciliary flush  Granulomatous vs. non‐granulomatous  Keratic precipitates  Fine  Unilateral vs. bilateral  Small, nongranulomatous  Granulomatous

Photo retrieved from http://www.uveitis.org Photo retrieved from http://www.medicinenet.com/image‐collection/uveitis_picture/picture.htm

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Standardized Grading Scales for Uveitis Other signs

 IOP  Low IOP due to decreased aqueous production in acute phases  High IOP often found in viral conditions (e.g. HSV keratouveitis)

 Peripheral anterior synechiae and posterior synechiae

 Iris atrophy

 Iris nodules

 Posterior involvement  Vitritis, optic neuritis, choroiditis, retinitis, and macular edema

Retrieved from http://www.reviewofoptometry.com/continuing_education/tabviewtest/lessonid/109524/

Etiology of Uveitis Anterior Uveitis

 Idiopathic  Infections  Syphilis  Breakdown of the blood‐aqueous‐barrier  Autoimmune  Tuberculosis  Non‐fenestrated blood vessels of the Major Arterial Circle of the Iris  JIA  Herpes zoster  Tight junctions (macula occludens) of non‐pigmented epithelium of ciliary  Ankylosing spondylitis  Herpes simplex  Ulcerative colitis  Adenovirus  35‐50% of cases are idiopathic  Crohn’s disease  Toxoplasmosis  Mild uveitis is expected after ocular surgery  Reiter’s syndrome  CMV  Lens induced  AIDS  Can be recurrent, recalcitrant, granulomatous or non‐granulomatous  Malignancy  Candida  Idiopathic is a diagnosis of exclusion  Retinoblastoma  Traumatic  Leukemia  Lymphoma  Malignant melanoma

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Intermediate Uveitis Posterior Uveitis

 Defined as intraocular inflammation that predominantly involves the peripheral  Defined as the breakdown of the blood‐retinal‐barrier retina, and vitreous  Tight junctions between RPE cells  Non‐fenestrated retinal blood vessels  Infectious –Ex. Lyme Disease  Infectious –Ex. Toxoplasmosis  Inflammatory –Ex. JRA  Inflammatory –Ex. Sarcoidosis  Infiltrative –Ex. Lymphoma  Infiltrative –Ex. Retinoblastoma  4‐17% of all uveitis  Many systemic causes  Anterior vitreous cells  Behcet’s, syphilis, SLE, TB, sarcoidosis

 Causes:  Many ocular diseases  63% ‐ unknown etiology  Toxoplasmosis, Eales’ disease  22% ‐ sarcoid  Common signs –retinal vasculitis  1% ‐ multiple sclerosis and Lyme disease

Photo retrieved from http://www.mvretina.com/education/images/SNOWBALLS_001.jpg Photo retrieved from http://www.myvisiontest.com/newsarchive.php?action=tag&id=152

Complications of Uveitis Lab Testing

 Development of chronic uveitis  Minimum lab testing  Complete blood count (CBC) with differentials  Macular edema  Erythrocyte sedimentation rate (ESR)  Angiotensin converting enzyme (ACE)  Ocular hypertension/glaucoma  Venereal disease research laboratory (VDRL)  Cataract formation  Fluorescent treponemal antibody absorption (FTA‐ABS)  HLA‐B27  Antinuclear antibody (ANA) test  Urinalysis  Chest X‐ray  PPD

Photo accessed from http://webeye.ophth.uiowa.edu/eyeforum/tutorials/cataract‐for‐Med‐Students/Page2.htm

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Lab Testing Treatment

 GOALS:  Therapeutic Treatments  Protect vision  Steroids  Reduce scarring  Topical  Reduce pain  Local  Decrease inflammation  Systemic  Find the cause  Cycloplegics  Analgesics  Immunosuppressants

Retrieved from http://www.reviewofoptometry.com/continuing_education/tabviewtest/lessonid/107773/ Photo retrieved from http://www.dragonflyeffect.com/blog/what‐is‐a‐good‐goal/

Treatment Treatment

 Topical steroids  Cycloplegics  Improve comfort, stabilize the blood aqueous barrier, and break synechiae  Pred Forte (prednisolone acetate 1%, Allergan) formation  Durezol (difluprednate 0.05%, Alcon)  5% b.i.d.  0.25% b.i.d.  Lotemax (loteprednol 0.5%, Bausch + Lomb)  1% b.i.d.  Aggressive use  1% t.i.d.  q1h to q.i.d. for 7‐10 days  Cycloplegic can be stopped when no pain or advancement of inflammation is reported/seen  Steroids should not be tapered until there is a two‐grade improvement in clinical signs and should not be stopped until  Non‐therapeutic treatments there is a complete resolution of all cells, flare, and macular  Hot compress edema  UV protection – sunglasses/hats  Stay indoors  Low lighting  Plus for near Photo retrieved from www.drug3k.com Photos retrieved from www.allergan.com and https://www.myalcon.com/products/pharmaceutical Photo retrieved from http://www.sandinfamily.com/ponograms/058‐a‐new‐outlook.htm

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Patient: RR

 63 year old African American female

 Ocular Hx:  Radial keratotomy (RK) OU ~ 35 years ago  Phacoemulsification with posterior chamber intraocular lens  OD –8/12/14  OS –7/22/14

 Medical Hx Case Report  High cholesterol  s/p Appendectomy  Two C‐Sections (1975 and 1979)

Photo retrieved from http://webeye.ophth.uiowa.edu/eyeforum/atlas/pages/RK‐radial‐keratotomy‐with‐tear‐star.html Photo retrieved from http://atleegleaton.com/procedures/cataract‐surgery/

Patient: RR Case History –9/13/14

 Family Hx:  CC: Severe pain and redness OS  Cataracts  Quality: Constant  Duration: 1 week  Gtts:  Timing: All day  Visine prn  Associated signs/symptoms: Blurry vision, watery eyes, light  Medications: sensitivity  ASA –81 mg qd p.o.  Context: Started while flying back on an 11 hour flight from the  Simvistatin –40mg qpm p.o. United Kingdom  Modifying factors: Preservative‐free artificial tears q1h and  Allergies: Systane gel qhs OU  Penicillin  Severity: 10/10  Seasonal allergies

Photo retrieved from http://www.petanswers.com/2013/05/20/episode‐12‐goopy‐eyes‐and‐why‐halve‐of‐all‐microchips‐are‐useless/

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Testing Ocular Health

 VA (sc):  OD: WNL  RE: 20/30+2 PH: 20/20‐1  LE: 20/80 PH: 20/70+1  OS: (After dilation)  IOP:  Conj: 3+ chemosis, 3+ injection  OD: 17 mm Hg  OS: 29 mm Hg  Cornea: 4 inc RK, 3+ Mutton‐fat KPs, 2+ diffuse PEK  A/C: D/1‐2+ cells  Pupils:  PERRL, (‐) APD  Lens/IOL: PC IOL clear  Vitreous: Quiet  EOMs:  Full/no restrictions  Fundus: “Hazy view”  Pain OS with eye movement

 CVFs:  FTFC OU Photo courtesy of Walter Whitley, OD

Assessment/Plan F/U Visit – 9/15/14

 Assessment:  Quality: Pain and redness is improving  Granulomatous anterior uveitis OS  Duration: 1.5 weeks  Pseudophakia OU  s/p RK OU  Location: OS

 Plan:  Associated signs/symptoms: Constant watering, blurry vision, light sensitivity  Start Durezol q2h OS and Cyclopentolate 1% t.i.d. OS  Continue preservative‐free artificial tears q1h OS and Systane  Gtts: Durezol q2h OS, cyclopentolate t.i.d. OS, PF ATs q1h gel qhs OS. OS, and Systane gel qhs OU  RTC 1‐2 days  Severity: 3/10

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Ocular Health OS Assessment/Plan

 VA (sc): 20/135 PH: 20/55‐2  Assessment:  Granulomatous anterior uveitis OS  IOP: 15 mm Hg  Pseudophakia OU  Conj: 2+ chemosis/2+ injection  s/p RK OU

 Cornea: 4 inc RK, 3+ Mutton‐fat KPs, Trace PEK  Plan:  Continue Durezol q2h OS and cyclopentolate 1% t.i.d. OS  A/C: D/1‐2+ cells  Continue preservative‐free artificial tears q1h OS and Systane gel qhs OS.  Lens/IOL: PC IOL  Order chest X‐ray  Vitreous: Quiet  Order labs: CBC, ESR, ANA, RPR, FTA‐ABS, ACE, Lysozyme, HLA‐ B27, RF  Fundus: “Hazy view”  RTC 4 days

Lab Results F/U Visit –9/19/14

 Chest X‐ray: Normal  Quality: Slight discomfort, no pain  CBC: WNL  Duration: 2 weeks  ESR: 11 mm/hour 0‐30 mm/hour

 ANA: None detected  Location: OS

 RPR: Non reactive  Associated signs/symptoms: Constant watering, blurry vision,  FTA‐ABS: Non reactive light sensitivity, new onset cold sore  ACE: 32 U/L 9‐67 U/L  Gtts: Durezol q2h OS, cyclopentolate t.i.d. OS, PF ATs q1h  Lysozyme: 19 ug/mL 9‐17 ug/mL OS, and Systane gel qhs OU  HLA‐B27: Negative   Rheumatoid Factor: 10 IU/mL 0‐14 IU/mL Severity: 0/10

Photo retrieved from http://patientadvocates.com/8‐predictive‐biomarkers‐you‐should‐ask‐your‐physician‐about

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Ocular Health OS Assessment/Plan

 VA (sc): 20/200 PH: 20/100  Assessment:  Granulomatous anterior uveitis OS –improving with treatment  IOP: 13 mm Hg  Possible low‐grade endophthalmitis OS  DDx: Propionibacterium acnes, HSV keratouveitis  Pseudophakia OU  Conj: 2+ injection  s/p RK OU

 Cornea: 4 inc RK, few fine inferior KPs, 3+ stromal edema  Plan:  Continue Durezol q2h OS  A/C: D/1+ cell, fibrin clump along inferior iris border  Discontinue cyclopentolate OS  Start Valtrex (valacyclovir) 1 gm t.i.d. x 1 week  Lens/IOL: PC IOL  Continue preservative‐free artificial tears q1h OS and Systane gel qhs OS.  Refer to retinal specialist for consult/treatment  Vitreous: Quiet  RTC prn

Retinal Consult F/U Visit –1/28/14

 Assessment:  Quality: No pain, dry eyes  Endophthalmitis OS  Stromal corneal edema OS  Duration: 4 months  Pseudophakia OU   s/p RK OU Location: OS

 Plan:  Associated signs/symptoms: Intermittent watering  Intravitreal vancomycin/ceftazidime OS  Gtts: Durezol b.i.d. OS  Vitreous tap/biopsy OS –Lab results negative  OCT Macula –No evidence of macular edema or subretinal fluid  Severity: 0/10  Decrease Durezol b.i.d. OS, start Latanoprost qhs OS  F/u with Eye Care Associates of Nevada, RTC 6 months

Photo retrieved from http://www.imagekb.com/retina

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Ocular Health OS Assessment/Plan

 VA (sc): 20/55+1 PH: 20/25+2  Assessment:  IOP: 15 mm Hg  Post‐operative uveitis OS

 Conj: Quiet  Pseudophakia OU  Posterior capsular opacification OS>OD  Cornea: 4 inc RK, 2+ inferior endothelial pigment  s/p RK OU  A/C: D/Q

 Lens/IOL: PC IOL, 2+ PCO, pigment dusting on lens surface  Plan:  Continue Durezol b.i.d. OS (or Pred Forte 1% q.i.d. OS)  Vitreous: Quiet  Continue preservative‐free artificial tears q1h OS and Systane  C/D: 0.45 gel qhs OS.  Fundus: WNL  F/u with Retina in 6 months, RTC for YLC OS

Differential Diagnosis Clinical Pearls

 Herpes simplex virus (HSV) keratouveitis  Be aggressive with treatment

 Phacoanaphylaxis/lens‐induced uveitis  Don’t be too quick to taper

 Propionibacterium acnes endophthalmitis  Find the cause

 Treat and follow

 Refer to specialist as indicated

Photo courtesy of Walt Whitley, O.D.

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References

 About Uveitis. Canadian Uveitis Society. 2015. Available at https://canadianuveitissociety.com. Accessed March 27, 2015.

 Anesi SD, Foster CS. Anterior uveitis: etiology and treatment. Advanced Ocular Care. 2011 Feb: 32‐4. Available at: http://eyetubeod.com/2011/02/anterior‐uveitis‐etiology‐and‐treatment. Accessed March 29, 2015.

 Bloch‐Michel E, Nussenblatt RB. International Uveitis Study Group recommendations for the evaluation of intraocular inflammatory disease. Am J Ophthalmol. 1987 Feb 15;103(2):234‐5.

 Foster CS, Davanzo R, Flynn TE, et al. Durezol (Difluprednate Ophthalmic Emulsion 0.05%) compared with Pred Forte 1% ophthalmic suspension in the treatment of endogenous anterior uveitis. J Ocul Pharmacol Ther. 2010 Oct;26(5):475‐83.

 Gutteridge IF & Hall AJ. Acute anterior uveitis in primary care. Clin Exp Optom. 2007 Mar;90(2):70‐82.

 Jabs DA, Nussenblatt RB, Rosenbaum JT; Standardization of Uveitis Nomenclature (SUN) Working Group. Standardization of uveitis nomenclature for reporting clinical data. Results of the First International Workshop. Am J Ophthalmol. 2005 Sep;140(3):50916.

 Kabat AG. Uveitis. In: Bartlett J, Jannus S (eds.). Clinical Ocular Pharmacology. 3rd ed. St. Louis: Elsevier; 2008:587.

 Uveitis. The Ocular Immunology and Uveitis Foundation. 2015. Available at http://www.uveitis.org/patients/education/glossary. Accessed March 28, 2015.

 Whitley W, Shephard J. The Basics of Uveitis. Review of Optometry. 2011 August. Available at http://www.reviewofoptometry.com/continuing_education/tabviewtest/lessonid/107773/. Accessed March 27, 2015.

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Ocular Indications for Case Report Carotid Imaging 63 YOM CC: change in vision OS x 2 weeks Tripped, hit chest on a table Upper ½ of vision appeared “fogged” Change was transient at first, then permanent No pain A review of the clinical of carotid No right eye symptoms occlusive disease, imaging techniques, and treatment No recent change in medications or general health Did not change with posture or activity strategies. Ocular history: low , otherwise negative.

Medical history: osteoarthritis, BCC, PTSD, substance abuse, high cholesterol

Crystal Thanos, OD Medications: allopurinol, atorvastatin calcium, ibuprofen, indomethacin, lorazepam, metoprolol succinate, noritriptyline HCl, quetiapine fumarate Roseburg VA Medical Center 913 NW Garden Valley Blvd. Roseburg, OR 97471 [email protected]

Case Report

VA sc: OD 20/20, OS 20/40+2 PHNI

PERRL –APD, EOMs full and painless, confrontation fields full OD, constricted sup-nas OS

Slit lamp: unremarkable, trace NS OU

GAT: 16mmHg OD, 15mmHg OS

Posterior segment…

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Anatomy Review

The common carotid arteries (2) branch off the aorta and supply blood to the head and neck.

Carotid bifurcation External carotid – superficial head and neck Anatomy Review Internal carotid –brain and eye The blood supply to the eye http://healthfavo.com/carotid-arteries-netter.html

Anatomy Review Central Retinal Artery

Internal carotid branches: One of the first and smallest branches of ophthalmic artery

First = Ophthalmic artery Supplies blood to the retina and to the optic nerve via Central retinal artery collateral branches Other branches

http://www.slideshare.net/rawanayman/ophthalmic-artery

http://www.retinareference.com/anatomy/

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Circle of Willis

Anastomosis that supplies blood to the brain

In presence of stenosis or occlusion, cerebral perfusion is preserved

Carotid Artery Stenosis Causes and Effects

http://en.wikipedia.org/wiki/Circle_of_Willis

Carotid Artery Stenosis Carotid Artery Stenosis

Narrowing of the carotid Plaque can be stable or unstable arteries caused by Danger = reduced blood flow and potential for embolus release Accumulation of fat, Stroke cholesterol, Association with heart disease inflammatory cells, and Death cellular waste products Risk factors for carotid artery disease: on the inside of the Smoking arterial wall Hypertension Stiffening of artery wall Diabetes Obesity **Carotid bifurcation** http://www.mayfieldclinic.com/PE-CarotidStenosis.htm Sedentary lifestyle

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Ocular Manifestations Ocular Signs Symptoms Manifestations of Retinal emboli Amaurosis fugax Carotid Stenosis CRAO/BRAO Long-term vision loss Ocular ischemic Signs and Symptoms syndrome

Asymmetric diabetic or

Retinal Emboli Retinal Emboli

Type Appearance Origin Systemic A plaque-like structure Associations that has been released Cholesterol White or yellow, Internal carotid Atherosclerosis into the arterial (Hollenhorst) shiny, refractile, artery, carotid circulation, often from usually seen at bifurcation, carotid artery artery bifurcation ophthalmic artery, or aortic arch Can get lodged in the lumen of small retinal Calcific Large, dull, white Cardiac valves Myocardial mass near the infarction, mitral arteries optic disc. Often valve stenosis, causes CRAO or atrial fibrillation Can cut off blood flow BRAO distally Platelet-Fibrin Long, dull-gray, Ulcerated Atherosclerosis

http://www.reviewofoptometry.com/content/d/retina/c/41409/ easily fragmented, cholesterol move quickly plaques in the through arteries carotid artery

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Retinal Emboli Retinal Artery Occlusion Calcific Cholesterol (Hollenhorst) Branch Central

http://stroke.ahajournals.org/content/39/4/1371.figures-only

http://www.reviewofoptometry.com/content/d/retina/c/ 41409/ Platelet-Fibrin

http://www.odcareer.com/retinal-artery-occlusion-and-stroke/

http://coloradoretina.com/information/retinal-vascular-diseases/

http://www.reviewofoptometry.com/content/d/case _report/c/32672/

1/12/15 – two weeks after onset of 1/21/15 symptoms

Example: Course of a Branch Retinal Artery Occlusion My patient’s fundus photos over time 2/12/15 3/19/15

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Asymmetric Diabetic or Hypertensive Retinopathy Chronic ischemia to the Symptoms/Signs: eye and orbit Slow vision loss PDR in one eye, none-mild NPDR in the other = Pain severe carotid stenosis on one side Episcleral injection Which side has the stenosis? 50/50 Narrow arteries Hypertensive retinopathy in one eye, none in the other Dilated, irregular, non- tortuous veins = severe stenosis or occlusion on the side ipsilateral to **Mid-peripheral retinal “normal” looking eye hemorrhages** NVI (late)

http://imagebank.asrs.org/discover-new/files/5/25?q=ocular%20ischemic%20syndrome

Ocular Manifestations Amaurosis Fugax

Signs Symptoms Latin and Greek: “fleeting Many causes! Most Retinal emboli Amaurosis fugax darkening” common is ischemia to the retina or optic nerve CRAO/BRAO Long-term vision loss Area of blank, gray, or fuzzy vision Defect is altitudinal when Ocular ischemic ischemic in origin syndrome Lasts seconds to minutes. Then, vision returns to DDx: transient visual Asymmetric diabetic or normal. obscuration (TVO) hypertensive retinopathy

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Permanent Vision Loss

Prolonged ischemia can result in permanent loss of function of the affected retina The Statistics BRAO, CRAO Why these ocular findings matter Presence of a cilioretinal artery?

http://imagebank.asrs.org/file/2882/central-retinal-artery-occlusion-cilioretinal-artery-sparing

Prevalence of Asymptomatic More Statistics Retinal Emboli Beaver Dam Eye Study – Beaver Dam, Wisconsin Older age and male = more emboli, more strokes 4,926 subjects age 43-86 18% with asymptomatic emboli had stenosis >60-75% 1.3% prevalence at baseline (1988-1990) Almost 3x increased risk of stroke-related death within 8 years Stroke rate: 8.5% annually in those with asymptomatic emboli, 0.8% without emboli Blue Mountains Eye Study – Australia 3,654 subjects age 49 and older 20-60% with amaurosis fugax have stenosis >50% 1.4% prevalence at baseline (1992-1994) Visible embolus along with RAO does not influence likely Both: Asymptomatic emboli were associated with smoking (past and amount of stenosis current), HTN, and vascular disease

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Carotid Ultrasound Basics

Carotid Duplex: B-mode Other options: and Doppler ultrasound cerebral angiography (invasive, expensive, risk Detect plaques and of complication) increases in blood flow magnetic resonance velocity angiography (MRA) Higher velocity = greater (more expensive, time stenosis consuming, some contraindications) Noninvasive, safe, Carotid Workup inexpensive, quick Basics of Carotid Ultrasound

Carotid Stenosis Grading Negative Carotid Ultrasound

NASCET (1991): Stenosis percentages Clinically significant Important to rule out Mild: <50% based on: stenosis is not always source that could put the Moderate: 50-69% ICA peak systolic found with ocular signs patient in danger velocity (PSV) Severe: >70% My patient: Biggest concerns are Visibility of plaque Near-occlusion 17-49% stenosis on the stroke, risk for associated Occluded: 100% right heart failure, death Others? ~49% on the left, some soft plaque

Next steps: cardiac or neuro consult

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Treatment

Medical Endarterectomy

Aspirin (81-325mg/day), Removal of plaque with antithrombotics goal to reduce stroke risk

May progress to Risks: debris anticoagulants such as embolization, TIA and warfarin (Coumadin) stroke, surgical and Quick Summary of anesthesia risks Treatment Options Endarterectomy vs. Medication

Endarterectomy Eligibility Summary

Symptomatic Stenosis Asymptomatic Stenosis 1. Patient presents with ocular signs/symptoms No benefit for stenosis <50% Endarterectomy only for medically stable patients 2. Alert PCP, order carotid duplex Mild reduction in 5-year with 80%+ stenosis, a. Result is not significant stenosis: cardiac, neuro workup stroke risk for moderate (50- expected to live 5+ years, 69%) stenosis b. Result is + stenosis: and in surgical centers i. Do nothing with <3% complication Greatest benefit for patients ii. Medically treat with stenosis >70%, males, rate iii. Surgically treat history of stroke in past 3 months, and patients with 3. hemispheric TIA Appropriate optometry follow-up to monitor for changes NOT indicated for occluded ** “Benefit” = decreased risk of arteries stroke

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References

Barnett HJ, Taylor DW, Eliasziw M, et al. For the NASCET Grant EG, Benson CB, Moneta GL, et al. Carotid artery stenosis: collaborators. Benefit of carotid endarterectomy in patients with gray-scale and doppler US diagnosis – Society of Radiologists in symptomatic moderate or severe stenosis. N Engl J Med Ultrasound Consensus Conference. Radiology 2003;229:340-346. 1998;339(20):1415-25. Klein R, Klein BE, Jensen SC, et al. Retinal emboli and stroke: the Benavente O, Eliasziw M, Streifler JY, et al. for the NASCET Beaver Dam Eye Study. Arch Ophthalmol 1999;117:1063-1068. collaborators. Prognosis after transient monocular blindness associated with carotid artery stenosis. N Engl J Med McCullough HK, Reinert CG, Hynan LS, et al. Ocular findings as 2001;345(15):1084-90. predictors of carotid artery occlusive disease: Is carotid imaging justified? J Vasc Surg 2004;40:279-286. Biouse V, Trobe JD. Transient monocular visual loss. Am J Ophthalmol 2005;140:717-722 Mitchell P, Wang JJ, Li W, et al. Prevalence of asymptomatic retinal emboli in an Australian urban community. Stroke. Chen CS, Franzco, Miller NR. Ocular ischemic syndrome: review 1997;28:63-66. of the clinical presentations, etiology, investigation, and management. Comp Ophthalmol Update 2007;8:17-28. Sacco RL. Extracranial carotid stenosis. N Engl J Med 2001;345(15):1113-1117. Cugati S, Wang JJ, Rochtchina E, Mitchell P. Ten-year incidence of retinal emboli in an older population. Stroke. 2006;37:908-910. Sharma S, Brown GC, Pater JL. Cruess AF. Does a visible retinal embolus increase the likelihood of hemodynamically significant Dodick DW, Meissner I, Meyer FB, Cloft JH. Evaluation and carotid artery stenosis in patients with acute retinal arterial management of asymptomatic carotid artery stenosis. Mayo Clin occlusion? Arch Ophthalmol 1998;116:1602-1606. Proc 2004;79(7):937-944. Spalton DJ, Hitchings RA, Hunter P (1993). Atlas of clinical Donnan GA, Davis SM, Chambers BR, Gates PC. Commentary: ophthalmology (2nd ed.). St. Louis: Mosby International Ltd. surgery for prevention of stroke. The Lancet 1998;351:1372-1373. Wang JJ, Cugati S, Knudtson MD, et al. Retinal arteriolar emboli Fields CR. Carotid artery occlusive disease: systemic and ocular and long-term mortality. Stroke. 2006;37:1833-1836. manifestations, diagnosis and treatment. The Southern Journal of Optometry 1997;14(3):19-28. Wong TY, Klein R. Retinal arteriolar emboli: epidemiology and risk of stroke. Curr Opin Ophthalmol 2002;13:142-146. Gerstenblith AT & Rabinowicz MP (2012). The Wills eye manual: Office and emergency room diagnosis and treatment of eye disease (6th ed.). Philadelphia, PA: Lippincott Williams & Wilkins.

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Reminders of OCT interpretation

 OCT image is obscured by:  Pigment Brandon McFadden, OD  Blood Mann-Grandstaff VA Medical Center  Fibrosis  Artifacts  Mirroring  Blinking  Movement  Tips for taking images:  90D view on fundoscopy, OCT may be possible

Choroidal Nevus vs Ocular Small Nevus Melanoma  Identifying risk factors of melanoma3  To Find Small Ocular Melanoma Using Helpful Hints Daily ○ Thickness greater than 2mm ○ Subretinal Fluid ○ Symptoms ○ Orange Coloration (lipofuscin) ○ Distance from Optic Nerve Head within 2DD ○ Ultrasound Hollowness ○ Absence of Halo ○ Absence of Drusen ○ Size

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Large Peripheral Nevus Large Peripheral Nevus

Large Elevated Nevus Large Elevated Nevus

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Large Elevated Nevus Large Elevated Nevus

Large Elevated Nevus Elevated Nevus

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Elevated Nevus Nevus with Subretinal Fluid

3 Small Choroidal Melanoma Nevus with Subretinal Fluid Nevus Findings RPE Changes Normal 3% Atrophy 95% Nodular 3% Absent 0% Subretinal Fluid 92%

Choroidal Nevus RPE Changes Normal 35% Atrophy 43% Nodular 8% Absent 4% Subretinal Fluid 16%

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Chorioretinal scar Retinal Hole

Retinal Hole Macula-Off Retinal Detachment

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Chronic Detachment Retinoschisis

Retinoschisis Retinoschisis

Image from Kanski et al Image from Kanski et al

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Retinoschisis Vitreous Hemorrhage

Vitreous Tuft Macroaneurysm

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Hemorrhagic PVD

References

1. Shields CL, Shields JA, Kiratli H, De Potter P, Cater JR. Risk factors for growth and metastasis of small choroidal melanocytic lesions. Ophthalmology. 1995;102:1351–61 2. Ghassemi F, Shields CL, Materin MA, Shields JA. Small Choroidal Melanoma with Monosomy 3. Middle East African Journal of Ophthalmology. 2010;17(3):268-269 3. Shields CL, Furuta M, Berman EL, et al. Choroidal Nevus Transformation Into Melanoma: Analysis of 2514 Consecutive Cases. Arch Ophthalmol. 2009;127(8):981-987. 4. Kanski, Jack J., and Brad Bowling. Clinical Ophthalmology a Systematic Approach. 7th ed. Edinburgh: Elsevier/Saunders, 2011. Print.

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CASE PRESENTATION BILATERAL CONGENITAL • 6 year-old Hispanic male SUPERIOR OBLIQUE PALSY: • First eye exam at 5 months-old due to concern of left eye turning in A CO-MANAGED APPROACH • No history of head trauma Stacy J. Hill, OD • Caesarian birth without complications Pediatrics and Vision Rehabilitation Resident Pacific University College of Optometry • Over 20 exams from 5 months up to 6 years-old

• Large angle esotropia: OS

• High Compound Hyperopic Astigmatism OU

CASE PRESENTATION CASE PRESENTATION

• Habitual SRx: • Age 4-5 years old, after h/o wearing the Bangerter foil • OD: +6.50 -3.25 x023 • OS: +6.25 -2.75 x145 • VA more within 1-2 lines consistently

• EOMS: 3+ RIO, 3+ LIO • 8-10 LE(T) + DVD

• h/o Mild Amblyopia OS: 2-3 line visual acuity difference between eyes • EOMS: 3+ RIO, 3+ LIO

• Tx 4 month • +RDS on multiple visits at near, but sometimes no stereo due to OS suppression

• Moderate Right or Dissociated vertical deviation (DVD) • OS Suppression beyond 1 m on worth 4 dot on other visits

• Fusion vs OS suppression • Vertical prism attempted without change to fusion

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6 Y/O: PEDS CVE 2014 PRESURGICAL VIDEO

• Visual Acuity (CC): • Distance: 20/20 OD; 20/40+ OS; 20/20- OU • Near: 20/25- OD, 20/32+ OS • Pinhole OS: 20/30+ • OS VA confirmed with symbols

• Randot Stereo: (-)Forms, 1/3 animals (400”)

• Pupils, Confrontation Visual Fields, anterior and posterior health normal

• Final SRx • OD: +6.50 -3.50 x026 • OS: +6.25 -2.75 x145

PRESURGICAL VIDEO 6 Y/O: PEDS CVE 2014 • EOMs:

• OD: 3+ IO, 2- SO

• OS: 3+ IO, 2- SO

• Cover Test at near: Strong V-Pattern

• Primary: small Alt ET with OD fixation preference, RHT

• Upgaze: 12 Alt XT, RHT

• Downgaze: 18 Alt ET, RHT

• No head tilt

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DIFFERENTIAL DIAGNOSES PRESURGICAL EVALUATION • Congenital vs Acquired? • EOMs: asymmetric presentation: abduction of eye in inferior oblique DAF OD, OS • rule out trauma and neoplasm • OD: 3-4+ IO, 2-3- SO • OS: 2-3+ IO, 2- SO • Hypertropia vs Dissociated Vertical Deviation • Cover Test: large V-pattern with RHT in primary gaze, reversing hyper in differing gazes proportionate to overaction of IO, OD fixation preference • Hypertropia OD alternating with hypotropia OS (12 Alt XT, RHT?) (poor fixation) • DVD would have asymmetric presentation without hypo • Or could have a hypertropia in addition to a DVD

30 Alt ET, 8 LHT 18 Alt ET, 12 RHT 16 Alt ET, 30 RHT • CN IV (Superior Oblique) Palsy: unilateral vs bilateral

• CN VI () Palsy 20 Alt ET, 14 RHT • CN III () Palsy

DIFFERENTIAL DIAGNOSES • Primary Inferior Oblique overaction (secondary to infantile esotropia)

• Not a true vertical

• Esotropia

• Monocular vs Alternating with fixation preference

• Constant vs intermittent

• Accommodative

• V pattern

• Thyroid-related ophthalmopathy

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EXTRAOCULAR MUSCLES EXTRAOCULAR MUSCLES Extraocular Muscles Primary Action Secondary Action Tertiary Action

Lateral Rectus Abduction None None

Medial Rectus Abduction None None

Superior Rectus Elevation Incyclotorsion Adduction

Inferior Rectus Depression Excyclotorsion Adduction

Superior Oblique Incyclotorsion Depression Abduction

Inferior Oblique Excyclotorsion Elevation Abduction

EXTRAOCULAR MUSCLES EXTRAOCULAR MUSCLES

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SUPERIOR OBLIQUE PALSY UNILATERAL SUPERIOR OBLIQUE PALSY • Most common cause of vertical/cyclovertical ocular deviation • Parks 3-step “marching” pattern: for relatively new palsy

• 29-66% congenital • Right-left-right or left-right-left • 1st: which eye is hyper? • Unilateral or bilateral (up to 29%) • 2nd: which gaze has worse hyper? • Paretic eye is higher regardless of which eye is fixating • 3rd: which tilt has worse hyper? • Creates a “falling eye” of the non-paretic eye when the paretic eye fixates • Paretic eye is hypertropic/hyperphoric • Can be phoric or tropic depending on compensatory mechanisms • Hyper is worse in opposite gaze than ipsilateral gaze • Torsion: excyclotorsion of the paretic eye: may or may not be perceived • hyper increases when paretic eye is adducting • Why? Inferior oblique is overaction secondary to superior oblique • Vertical vergences palsy. • Congenital expect larger than normal compensatory vertical vergences • Hyper is worse in ipsilateral head tilt (+ Bielschowsky) • Head tilt away from affected side to compensate for vertical and torsion • Deficient ability to depress

UNILATERAL SUPERIOR OBLIQUE PALSY BILATERAL SUPERIOR OBLIQUE PALSY • Spread of Concomitancy • Estimated up to 25-29% in various articles • Over time may measure as “concomitant” due to secondary changes to • Bilateral cases tend to be asymmetric and the eye with the more significant SOP muscles may mask the SOP of the lesser affected eye • Hyper eye: superior rectus and inferior oblique contracture and atrophy • Can also get changes in the fellow eye • Look carefully for any superior oblique underaction/ inferior oblique overaction in the non-hyper eye • Ocular Torticollis: more common in congenital • Neck and back tightness and pain due to abnormal head posture • Bilateral SOP is almost always due to closed head trauma • Habitual head tilt (to align eyes vertically and match excyclotorsion) toward the opposite shoulder with head turn to put eyes in ipsilateral gaze (to minimize • Cover Test: Exo in upgaze, Eso in downgaze (V-pattern ET) vertical separation) • EOMs: Superior oblique underaction OU (often asymmetric) with Inferior oblique • Can prescribe vertical prism to try to overcome deviation to prevent head tilt, overaction; inferior oblique may overact to the point of abducting the eye instead but head tilt is often related to torsion of elevating • No prism can correct torsion

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TROCHLEAR NERVE BILATERAL SUPERIOR OBLIQUE PALSY

• Subjective complaints of torsion

• subjective excylotorsion is >10 degrees (worse in downgaze)

• Often no habitual head tilt

• Instead, use chin-down posture (to neutralize deviation)

• Positive Bielschowsky’s head tilt test on each side

• RHT on right tilt

• LHT on left tilt

SUPERIOR OBLIQUE PALSY SUPERIOR OBLIQUE PALSY • Non-surgical: TREATMENT OPTIONS • Non-surgical: TREATMENT OPTIONS • Prism • Vision Therapy • Difficult to use if still deviation is still nonconcomitant. • Success depends on the magnitude of the deviation/extent of the • If correct for primary gaze, contralateral gaze will need more prism and palsy ipsilateral gaze will need less prism • Develop horizontal ranges to help control vertical deviation • Doesn’t treat torsion • Head tilt when diplopic: often diplopic at end of the day • Develop compensatory vertical vergence ranges • May develop secondary muscle changes: • Torsion therapy limited: may result in periodic head tilt and • hyper eye will stay hyper for long period of time will cause spread of neck/back issues if angle decompensates concomitancy if SR contracture occurs and then easier to tx with prism • May decompensate with age • Monovision: SRx or CLs • Suspend an image • often SOP manifests diplopia around early-presbyopia in untreated patients • Use hyper eye for reading to prevent SR contracture • Occlusion (ex. Contact paper, CL)

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SUPERIOR OBLIQUE PALSY STRABISMUS SURGICAL MANAGEMENT TREATMENT OPTIONS • Strabismic Surgical Management: Considerations • Sensory status and fusion potential • Surgical: • Suppression: deep vs shallow, peripheral vs central • Mechanical repositioning of the EOMs altering effective actions on the • Amblyopia globe • Anomalous Correspondence • Normalize the versions of the eyes which should automatically reduce • Eccentric Fixation the deviation (effectively balance the actions of the EOMs) • First degree, second degree, third degree fusion potential • Only way to correct torsion • Symptoms: diplopic, reduced binocularity, asthenopia, cosmesis, significant • Eliminate need for compensatory head tilt ocular torticollis • Can correct A or V pattern deviations with transpositions • Surgeon note: Poor control of eye turn more likely to have surgery • Can treat asymmetrical deviations by asymmetrical surgery to help • especially if symptomatic or risk of amblyopia or limiting binocular normalize each eye development

STRABISMUS SURGICAL MANAGEMENT PATIENT EDUCATION • Strabismus surgery risks: very rare • Outpatient procedure with local or general anesthesia • Anesthesia • most adults prefer general anesthesia • Diplopia • general anesthesia for all children • Need for second surgery: drift, under-correction, over-correction • Eye stays in the orbit • Sensory status • demonstrate on a model how close the muscles are to the front of the eye • Healing in an unexpected way • May operate on one or both eyes and one or more muscles to help restore balance between muscles and eyes • Rare Complications • Infection at surgical site/orbital cellulitis (if poor compliance with drops) • Small incision in conjunctiva • Allergy to suture • Identify muscle, isolate, and cut at attachment site • Endophthalmitis • Use caliper to measure correct amount to move muscle • Vision loss • Suture the muscle into its new position and close the wound • Lost muscle • Eye(s) will be red at incision site for ~2-3 weeks for kids; adults variable depending if adjustable suture is used (prolongs healing time)

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STRABISMUS SURGICAL TECHNIQUE POST-OPERATIVE MANAGEMENT OVERVIEW • Post-op instructions: • Pain management with ice packs and OTC pain meds • Recession: weakening a muscle action by moving it further back • Don’t rub eyes • Resection: strengthening a muscle action by moving it forward • Don’t go swimming x 1 week • Transposition: moving horizontal rectus muscles up or down to treat A or V pattern • Normal activities and visual behavior otherwise including showering deviation • Medication: • Harada-Ito: anterior and lateral displacement of anterior portion of superior oblique tendon for excyclotropia • Maxitrol (dexamethasone/neomycin/polymixin b) QID x 1 week • Anterior transposition: (such as with IO) weakens muscle action by moving insertion • Follow-up point anterior to the equator; treats asymmetric deviations • 1 day for adjustable suture only • Marginal myotomy(partial tenotomy): weakening an action of a muscle by reducing • 1 month visit for everyone the number of contractile muscle fibers; lengthens muscle • 6 months if adequate alignment/ 3 months if inadequate alignment/poor fusion • Superior Oblique Tuck: to strengthen SO action • Vision Therapy • Vertical muscle Tenotomy: for 1-4 pd vertical deviation • Train skills at new EOM positions and smaller angle of deviation • Vertical recession: for >4pd vertical deviation • Easier to treat suppression, improve fusion, and increase skills

POST-OPERATIVE ASSESSMENT CASE SURGICAL REPORT • Slit lamp exam • Procedures performed: • Incision site: redness, suture reabsorption • Bilateral Medial rectus recession, 3.5mm

• Refraction • Right Inferior Oblique recession with anterior transposition

• Check for axis shift (especially if surgery involves obliques) • Left inferior oblique recession, 10.0mm

• Cover Test and EOMs • Abbreviated: BMRc 3.5, RIOc/ant, LIOc10.0 • May get unusual results due to changed location of EOMs • Findings • Measurements will change as patient heals • Right inferior oblique was very tight and the left inferior oblique was moderately • Fusion testing (e.g. Stereopsis/Worth 4-dot/Amblyoscope/red lens) tight. Both were somewhat hypertrophic as well. The medial rectus muscles were • Double Maddox Rod for torsion: primary gaze and downgaze mildly tight but normal in appearance.

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3.5 WEEK POSTOPERATIVE MEASUREMENTS 4.5 WEEK POSTOPERATIVE MEASUREMENTS WITH SURGEON RETURN TO OUR CLINIC: PRE-VISION THERAPY MEASUREMENTS • VA: OD: 20/25-, OS: 20/50-/+ • VA: 20/40+1 OD, 20/50+2 • EOMs: 2+ LIO, 1.5- RSO, 1.5- LSO • EOMs: 2- RMR, 1.5-RSO; 1.5-LSO, 2+ IO • Cover Test: • No Stereo on Lang II or Randot • Primary gaze: 3 Alt ET, 4 LHoT (builds to 6 LHoT) • Worth 4 Dot: Deep OS peripheral suppression (2 dots seen at near in dark room) • XT in upgaze • Distance Cover Test: OD fixation preference • appears to have more Left hyper tendency on EOM, but definitely right hyper on • Primary Gaze: 3 Alt ET, 2 LHoT CT • Upgaze: 5 Alt XT • No stereo • Downgaze: 12 LET, 2 LHoT • Assessment: good initial postop alignment, unequal VA when previously • Right Gaze: 10 LET, 2 LHoT nearly equal, uncertain binocular potential • Left Gaze: 4 LET, 6 L LHoT • Right Tilt: 5 LET, 4 LHoT • RTC 6 weeks • Left Tilt: 5 LET, 3 LHT (REVERSAL OF HYPER) • Near Cover Test Primary Gaze: 5 Alt XT

5.5 WEEK POSTOPERATIVE MEASUREMENTS RETURN TO OUR CLINIC: PRE-VISION THERAPY MEASUREMENTS POSTOP VIDEO • VA: 20/25+ line, 20/20- letter OD 20/40+ line, 20/30+ letter OS • Habitual SRx: Dry Over-Ret Retinomax Updated SRx: +6.75 -3.50 027 +1.25 -1.00 x025 +6.75-4.00 x021 +7.50 -4.25 x023 +6.25 -3.00 x145 +1.25 -1.25 x150 +7.00 -3.25 x140 +7.00 -3.25 x143 • Red Lens: high frequency intermittent OS suppression, uncrossed diplopia intermittently with anti-suppression effort; unable to maintain diplopic image long enough to neutralize it • Amblyoscope: (OD decreased illumination) • First degree: (man and ladder):

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VISION THERAPY OVERVIEW

• Goals: • Amblyopia • Anti-suppression • Peripheral fusion • Primary gaze • Downgaze • Lateral gazes • Upgaze • Central fusion (guarded prognosis) • Estimated Treatment Time: 3-6mo

VISION THERAPY SUMMARY VISION THERAPY FROM 1-4 MONTHS FROM 1-4 MONTHS • Start patching OD 14 hrs per week(2 hrs per day) x 3 weeks • Red-Green TV Trainer: anti-suppression

• Bangerter foil (0.2) 14 hrs per week x 6 weeks • Amblyopia iNet: computer-based amblyopia treatment

• Bangerter foil (0.8) 14 hrs per week (currently x 2 weeks) (after 4 month post-op) • Morgenstern Litetrac Mazes: anti-suppression

• Red Print Michigan Tracking: Large font size decreasing font size: amblyopia tx • Projected Quoits Variable Vectogram at distance: peripheral distance fusion

• Amblyoscope training: anti-suppression and attempt fusion and vergences

• Single Oblique Mirror Stereoscope: anti-suppression • VTS4 computer-based program : RDS and stereo targets: central and peripheral fusion and vergences • Sherman Cards: promote alternating suppression/no suppression • Brock String: push-up, push-away: anti-suppression, fusion, and near vergences

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4 MONTH POSTOPERATIVE MEASUREMENTS 8TH VT SESSION/PROGRESS EVALUATION #1 BILATERAL SUPERIOR OBLIQUE PALSY: TAKE AWAY • VA: 20/25 line, 20/20-3 letter OD 20/30+1 line, 20/20-3 letter, 20/25-2 contour OS • EOMs: 1+ RIO; 2.5+ LIO with abduction OS in DAF of LIO, 1- LSO • Minimal/no hyper in primary gaze • Stereo: no stereo on Lang II or Randot • Hyper reversing in diff gazes (RHT in left gaze, LHT in right gaze) • Worth 4 Dot: OS suppression at all distances in full illumination • Significant V-pattern fusion from near to 3 ft with OS suppression beyond 3 ft in dark • Significant torsion • Distance Cover Test thru habitual SRx: • IO overaction, SO underaction • Primary: 2 LX(T) • Surgery for torsion • Upgaze: 12 LXT • Downgaze: 8 LET, 3 LHT (Left hyper) • Right Gaze: 2 XP, 4 RHP (Right hyper) • Left Gaze: 2 Alt. XT, 4 RHT/LHoT (Right hyper/Left Hypo) • Right Tilt: 6 LHoT (Left Hypo) • Left Tilt: 2 LX(T), 2 LH(T)

REFERENCES THANK YOU! • Retrieved 06/07, 2015, from http://what-when-how.com/wp-content/uploads/2012/04/tmp15F39.jpg • Caldeira JA. V-pattern esotropia: a review; and a study of the outcome after bilateral recession of the : a retrospective study of 78 consecutive patients. Binocul Vis Strabismus Q. 2003;18(1):35-48; discussion 49-50. Review. PubMed PMID: 12597768. • Pacific University staff and faculty • Helveston EM, Krach D, Plager DA, Ellis FD. A new classification of superior oblique palsy based on • Dr. JP Lowery congenital variations in the tendon. Ophthalmology. 1992 Oct;99(10):1609-15. PubMed PMID: 1454330. • Helveston EM, Oberlander M, Evan A, Connors B, Clendenon J. Ultrastrucure of the superior oblique tendon. • Dr. Richard London J Pediatr Ophthalmol Strabismus. 1995 Sep-Oct;32(5):315-6. PubMed PMID: 8531037. • London, R. (1992). An alternative approach to interpretation of the vertically acting extraocular muscles: • Dr. Graham Erickson Excerpts from the writings of arthur jampolsky. Problems in Optometry, 4(4), 556-564. • Dr. David Wheeler • Lynch, P. (1996). CN 4 graphics. Retrieved 06/02, 2015, from http://www.yale.edu/cnerves/cn4/cn4_graphics/cn4_1.gif • Jon Hill • Rutstein, R. P. (1992). Superior oblique palsy. Problems in Optometry, 4(4), 607-621. • 2014-2015 residents • von Noorden, G. K. (1980). and ocular motility: Theory and management of strabismus (2nd ed.). St. Louis, MO: C.V. Mosby Company. • von Noorden GK, Murray E, Wong SY. Superior oblique paralysis. A review of 270 cases. Arch Ophthalmol. 1986 Dec;104(12):1771-6. PubMed PMID: 3789976. • Wong, A. M. F. (2007). Eye movement disorders (1st ed.). New York, New York: Oxford University Press.

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Homonymous hemianopia

Case‐series of Homonymous or • The loss of half the visual field in both eyes on the Altitudinal Hemianopia same side, contralateral to the lesion • Caused by postchiasmal lesions, most commonly by Management Using Prism stroke (70%), trauma (14%), and tumors (11%)8 • ~60.5% of stroke patients might present with some cortical visual impairment, and 35% of those Rachel B. Lee, O.D. present with HH1 Primary care resident • Other causes include cerebral hypoxia, lobectomies, VA Portland Health Care System infections or neurodegenerative diseases

HH: Impact on daily function Prism

• Difficulty detecting obstacles on the side of the loss • Most common “substitutive treatment techniques” for • Locomotion disabilities especially when outdoors8 homonymous hemianopsia9 8 • Impaired visual search or orientation : • Aim to improve one’s mobility by providing more useful • smaller saccades, longer fixations information about obstacles and hazards • Impaired reading: omission of letters or lines, longer • Fit with the base toward the blind side. Images from the reading time blind field are shifted to patient’s seeing field • Inability to drive • 1Δ = 0.57 ̊ displacement • Increased risk of falls10

Reduced quality of life

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Prism VF Enhancement vs. Expansion

• Good candidates: • Good visual acuity • Enhancement: using prism to enhance the use of • Poor travel skills after stroke remaining field • Poor candidates: • The area shifted into a view of prism is no greater than • Hemi‐spatial neglect the amount of unaided view • Ignoring the sensory information from half of the body or surrounding 7 • Sector or round prism • Oculomotor deficits • Expansion: the total field available at any given direction • Cognitive decline of gaze is larger than the field available without prism • Prior field damage • EP prism

Sector/round prism Sector/round prism

• Requires scanning technique into the system which • Bilateral fit: one of the first designs for HH management results in an image jump • Prisms cover about full half of each lens • Intended for quick glances (large saccadic • Prism apices offset –no effect in the primary gaze movements) to locate objects • May cause apical scotoma • Increase in awareness due to the overlapping of the non‐sighted VF superimposed on the sighted VF 5 *Apical scotoma: • Binocular visual confusion: seeing two different a gap in the field of view views at the same apparent direction8 created by the last undeviated ray just outside the prism • Patient learn to identify the false image and make and the first deviated ray by quick head movements 9 the prism at its apex

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Sector/round prism Press‐OnTM Fresnel prism

• Trial with Fresnel (start with 15 then 20‐30Δ) to determine • Unilateral fit: more common the effectiveness before ordering ground‐in prisms • Fit on the temporal side of the carrier lens ipsilateral • Advantages: to the field defect • Inexpensive ($20) and lightweight • Can be placed on the nasal corner of the • Easily modifiable contralateral lens if patient’s eye on the side of • Could be used for scanning training the loss has profound visual impairment •Larger, more frequent eye movements toward the affected field area • Prism is applied away from the optical center of the • Disadvantages: lens, thus has no effect in primary position of gaze. • Reduced contrast –poor optical quality, decreased • The non‐prism eye compensate for the prism eye’s acuity, reflections and prismatic distortion5 apical scotoma3 • Needs to be replaced q 3 months • Post‐it note application

The Chadwick Hemianopia Lens The Gottlieb VFAS

• Previously known as InWaveTM lenses • 19mm (3.4”) diameter, 18.5Δ • Fabricated as straight edged segmented prism • Need 3‐4mm clearance in all directions • Thickness and weight of the prism controlled by the • Reduces thickness and weight when using the large small frame size frame • Ideal size: ≤18mm from apex of prism to temporal • Multifocals edge of frame • Wholesale: $350 • No multifocals • Wholesale: $350+

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Clinical trials ‐ VFAS Clinical trials ‐ VFAS

Gottlieb, et al. assessed the effectiveness of the Visual Field Awareness System (aka round, or button prism)5 Gottlieb, et al. 5 continued: • Published in 1992. • Questionnaires to assess visual field awareness before • Total 34 subjects from 1985 to 1988 and after the prism utilization • Used Visual Field Awareness Grid (similar to Amsler) • 19 accepted full‐time wear, and 8 accepted part‐ to document the VF awareness time wear = 79% acceptance rate • Results: • Bilateral prism placement: avg 1.5 ̊ improvement • Long‐term effectiveness (18 months): 9 continued full‐time wear, and 10 continued part‐ • Unilateral prism: avg. 14 ̊ improvement time wear. • Strabismic pt: prism placed in front of the fixating eye to avoid suppression

Clinical trials –VFAS & Driving Sector/round prism

Szlyk, et al. 11 (2005), done in IL • Compared Fresnel vs. Gottlieb VFAS (round prism) • Reasons for discontinuation: • 10 subjects (7 Left HH and 3 Right HH) received in‐office visual • Visual neglect performance training and on‐road driving training for 7 months • Improved scanning techniques from Fresnel prism • All subjects showed 13‐36% improvement within visual skills such as recognition, mobility, scanning, tracking and trial visual memory • Image jumps • No statistical differences between Fresnel and VFAS • Diplopia/confusion • At 2 year f/u (phone interview): • Cost • 6 patients still used the prism, 4 used frequently • 2 patients driving with prism • All patients used Gottlieb VFAS (better durability)

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Peripheral prisms –EP (Peli) Peripheral prisms –EP (Peli)

• Developed by Eli Peli, MSc, OD. in 2000 • Simultaneously expand ~20̊ of horizontal field in the • 8x22mm rounded rectangular prisms, could be fit above or below the limbus, or both upper and lower peripheral field at all direction of lateral gazes 2 • Available in 40Δ horizontal, 57 Δ horizontal & 57 Δ oblique • Fitted unilaterally on the side of the field loss • Noticeable at the primary gaze without scanning • Must select an adequate frame size into the prisms ≈ “multiplexing” • 12mm separation between prisms • Any prism‐induced diplopia, confusion or • Clearance of ≥3mm between prism and the carrier lens are confined to the periphery – better tolerated 2 • Multi‐focals could be utilized • Horizontal 40&57 Δ: $350 Oblique : $450

Peripheral prisms –EP (Peli) Peripheral prisms –EP (Peli)

• The community‐based trial (2008) showed similar or better success rate than those reported for monocular sector prism • Advantages: designs 3 • Field expansion essentially double of sector prism • Randomized crossover clinical trial of real and sham peripheral 4 • No central diplopia prisms glasses for hemianopia (2014) • Able to utilize bifocals • 64 patients, 2 periods of crossover (12 weeks) • Disadvantages: • At the end of the crossover, 64% selected real prisms over sham prisms (helpful for walking) • Confusion of images • No difference between horizontal and oblique designs • Difficulties with reading • Overall continuation rate a 6 moths: 41% • Problems with steps or curbs • Age found to be a weak predictor • Side and duration of hemianopia not predictive

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Why unilateral fit?

• The Cochrane systematic review states that the use of • Binocular rivalry favors sharper, high‐contrast images. visual rehabilitation lack high‐quality evidence. • Levelt’s law of binocular rivalry: “dominance of one • So far, clinical efficacy of the prism is based on eye’s image is inversely proportional to the strength patient’s subjective responses. of the other eye’s image”. • It is unknown if subjective improvement • Prism produced image is weakened in binocular corresponds with measurable behavioral competition with the direct view, but it is still able to improvement compete for visibility 6 • An obstacle or hazard is likely of higher contrast, and often moving, so has a better chance to be detected despite poor prism image quality

A randomized controlled trial to compare the clinical and cost‐effectiveness of prism glasses, visual search Compensatory training training and standard care in patients with hemianopia following stroke: a protocol • In addition to the optical aid, it is importance to connect Rowe, et al. the patients with the LV therapist and orientation & • 105 subjects split into three groups: mobility specialist10 • 40 sector Fresnel prism vs. visual search therapy vs. • Provide input on functional use of the prism control (advice only) adaptation10 • Aim to assess the effectiveness of interventions vs. • compensatory training standard of care • Systematic scanning strategies • VF measurement, reading, and functional measures • Reading training ***Completed trials in 08/2013

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Patient RB (67 y.o. AAM) Patient RB

Trial #1: Fresnel Sector prism 20ΔBO OS • Was able to navigate down the busy hallway without bumping into objects. Was able to describe objects on his left side correctly. Trial #2: EP prism OS • Left homonymous hemianopia secondary to right PCA • Patient was constantly looking left and tilting his head occlusion while navigating. Was more difficult to use. • MHx: L foot amputation, CAD with stenting, PVD s/p aortobifemoral bypass Released a trial pair of Plano specs with 20Δ BO Fresnel sector prism on the left lens • Wheelchair bound. His upper body is slightly tilted to the left side F/u: Trialed button prism which he also responded well.  Finalized Rx with the button prism

Patient TM (70 y.o. WM) Patient TM

Trial #1. 20 Δ Fresnel sector prism, BO left side of left lens • Increased awareness of objects on left side and was able to accurately identify the objects by shifting eyes into prism. Trial #2. EP prism placed 6mm superior to visual axis of left lens • Strong preference for this design and responded very • Left homonymous well. • MHx significant for h/o CVA x 4 • 2 months after the LV evaluation, patient suffered another stroke and was lost to follow up

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Patient JO (73 y.o. WM) Patient JO

• Fresnel prism (20 Δ base UP OD) • Patient demonstrated successful scanning techniques. Was able to detect objects and accurately • H/o L PCA stroke inferior to calcarine fissure (03/2014) and reach for objects in the superior field R PCA stroke inferior to calcarine fissure (06/2014) • At the f/u, patient stated that prism was too confusing • Large in macula and pallorous disc OS and would prefer to tip his head to see superiorly without clear etiology • BCVA 20/20‐2 OD, HM OS • Patient has great difficulty with O&M, falls frequently, and does not leave his house without his wife

Conclusion References

• Prisms improves one’s mobility by providing more useful 1. Ali, et al. Recovery from poststroke visual impairment: evidence from a clinical trials resource. information about obstacles and hazards in the blind field Neurorehabilitation, Neural Repair 27, 133‐141. 2. Apfelbaum, et al. Considering apical scotomas, confusion, and diplopia when prescribing prisms for homonymous hemianopia. Translational Vision Science & Technology. 2013;2(4) • It has potential to improve patient’s quality of life 3. Bowers, et al. Community‐based trial of a peripiheral prism visual field expansion device for hemianopia. Archive of Ophthalmology. 2008;126(5):657‐664 • However, fitting process could be time consuming and 4. Bowers, et al. Randomized crossover clinical trial of real and sham peripheral prism glasses for may involve 2‐4 training sessions depending patient’s hemianopia. Journal of the American Medical Association Ophthalmology 2014;132(2):214‐222 5. Haun and Peli. Binocular rivalry with peripheral prisms used for hemianopia rehabilitation. Ophthalmic & scanning abilities Physiological Optics. 2014;34:573‐579. 6. Gottlieb, et al. Clinical research and statistical analysis of a visual field awareness system. The Journal of • Majority of the latest articles are biased in favor of EP prism the American Optometric Association. 1992;64(8):581‐588 7. Lane, et al. Clinical trial options for patients with homonymous visual field defects. Clinical • Consider trialing both sector and EP designs Ophthalmology. 2008:2(1)93‐102 8. Perez, et al. Rehabilitation of homonymous hemianopia: insight into blindsight. Frontiers in Integrative Neuroscience. 2014. Vol. 8, 82 • Consider unilateral fit vs. bilateral 9. Plow, et al. Approaches to rehabilitation for visual field defects following brain lesions. Expert Reviews of Medical Devices. 2009:6(3)291‐305 • Connect the patient with the low vision therapist and O&M 10. Toffel, et al. Hemianopsia and falls prevention. AER online. 2012.1‐8. specialist for compensatory training 11. Szlyk, et al. Use of prisms for navigation and driving in hemianopic patients. Ophthalmic and Physiological Optics. 2005 25:128‐135

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CASES-CJ

INFANTILE (CONGENITAL) NYSTAGMUS NEW IDEAS ON TREATMENT

Connie Lee, OD Curtis Baxstrom, OD Vision Northwest Vision therapy, rehabilitation, and pediatric optometry

CASES-JB OBJECTIVE

 Nystagmus  Characteristics  Types- Infantile/congenital nystagmus  Etiology  Diagnostic tests/measurements  Developmental concerns  Treatment  Vision therapy treatment ideas  Cases  CJ  JB

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NYSTAGMUS UNDERSTANDING NYSTAGMUS

 What is nystagmus?  Waveform  Jerk, pendular waveform  Rhythmic, involuntary, oscillation of one or both eyes  Direction  Prevalence of nystagmus (all types) is about 24 in  Horizontal, vertical, torsional 10,000 and about 14 in 10,000 for infantile  Amplitude nystagmus from the Leicestershire nystagmus survey  <2 degree, 2-10, >10degrees  Frequency  Low (see-saw)  Medium (congenital)  Fast (spasmus nutans)  Conjugate/disconjugate  Constant/ intermittent  Symmetry/dissociation  Latency, Null point, Convergence

TYPES OF NYSTAGMUS/ CLASSIFICATION TYPES OF NYSTAGMUS/ CLASSIFICATION

 Committee for eye movement disorders and strabismus  Two main categories ( >35 different types of (CEMAS)  Physiological nystagmus nystagmus)  Vestibular  Infantile (congenital) nystagmus  Eccentric   Optokinetic appears in the first 3-6 months of life  Pathological nystagmus  Idiopathic, albinism, latent/manifest, spasmus nutans,  Infantile/congenital sensory nystagmus (afferent visual deficits), neurological  Fusion/latent and manifest forms  Spasmus nutans  Vestibular  Aquired nystagmus  Gaze holding deficiency  Disease of the visual system (brainstem and cerebellum)  Vision loss  Other pendular nystagmus/disease of central myelin  Vestibular imbalance  Ocular bobbing  Neurological/ CNS disease  Lid nystagmus  Fixational movments, saccadic intrusions, disturbance of saccades, smoth pursuit and vestibular eye movements  *CEMAS classification is not based on etiology and diagnosis

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INFANTILE/CONGENITAL NYSTAGMUS CEMAS INFANTILE NYSTAGMUS

 80% of nystagmus cases in childhood  Presents in first 3-6 months of life  Frequently associated with developmental sensory deficits  Usually horizontal in all positions of gaze, benign  No and not usually associated with CNS disease  Null point generally present  Nystagmus dampens with convergence

ETIOLOGY DIAGNOSTIC TESTS

 Idiopathic infantile nystagmus  Electrophysiological analysis and ocular motility  FRMD7 gene recording  Sensory in origin, ocular motor system development  Electrooculography  Albinism  Infrared reflectance oculography  Recessive autosomal genes  contact lens/ magnetic search coils  Retinal miswiring  Latent /manifest nystagmus  Infantile esotropia, congenital squint syndrome  Infantile nystagmus from afferent visual deficits (sensory in origin)  bilateral , congenital retinal dystrophies,  PAX6 mutations- foveal hypoplasia

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MEASUREMENTS IN CLINIC PRESENTING SYMPTOMS

 Document  Reduced vision, at distance > near  Qualities of the nystagmus  Convergence dampens nystagmus  Head posture/ torticollis/ head nodding  Impaired oculomotor control  Null point/ Convergence  Visual field and depth  Modified thorington  Focus/ attention span  Recordings  Head tilt, posture  Video (slow mo video), 20D lens  Developmental concerns  Readalyzer/ Visagraph  Impact visual development?  With associated conditions  ERG/VEP  Can we do something?  OCT (hand held)  Can we improve or cure?

TREATMENT TREATMENT

 Optimize visual acuity  Vision development  Correct or compensate refractive status?  Fix and follow  Contact lenses, low vision devices  Reaching for objects, crossing midline  Prism to null point  Accommodation

 stabilize optical image  Binocularity  Prism for convergence  Vision therapy for fixation stability  Dampen infantile nystagmus  Orthoptic  Therapy vs compensatory  Visual/auditory biofeedback

 Surgical considerations  Visagraph, readlyzer  Pharmacological/ Botox  Central/ peripheral awareness  Alternative treatment/ Acupuncture  Visual performance  Tachiscopic visual memory, peripheral processing

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NEW IDEA-VESTIBULAR POST-ROTATARY VISION THERAPY TREATMENT IDEAS NYSTAGMUS

 Convergence therapy  Close eyes and isolate horizontal  One may use prism to canals  rotate simulate positive fusional  produce post rotatory nystagmus in vergence then convergence  combination with existing nystagmus decreasing nystagmus  decreases BCVA due to combined  Compensatory vs therapeutic nystagmus  After image transfer  Patient then has to learn to dampen  Visual sensory feedback the nystagmus using a combination of  Near and far visual motor fixation, vergence, pursuits and activities, use proprioceptive saccades support for localization and  improve fixation control fusion

VESTIBULAR POST-ROTATARY NYSTAGMUS VESTIBULAR POST-ROTATARY NYSTAGMUS

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CASE CJ CASES-CJ

 2 year old African American Foster Child  Referred by Children’s therapy center to see if vision therapy would help with her visual functioning  Non verbal, non cooperative  Bilateral infantile left jerk conjugate nystagmus  Dampens with convergence, with a null point on lateral gazes  Likely secondary to optic nerve hypoplasia (Sensory in origin?)

 Possible treatment?

CASES-CJ CASES-CJ

 +0.50 OU opens awareness to periphery  BCVA 20/128 OD, OS with cardiff cards  Possible prism to null point or convergence?

 Visual vestibular therapy  Head posture and nystagmus control

 Visual/auditory biofeedback  After image transfer

 Eye hand coordination activity  Engage in visual surrounding  Sound sound +light  light  large objects

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CASES-CJ AFTER 6 MONTHS CASES-CJ COMPARISON

CASES-CJ AFTER 6 MONTHS CASES-JB

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CASES-JB CLINICAL PEARLS

 Down syndrome with infantile nystagmus  Nystagmus  Latent? Idiopathic?  Observation/documentation  Bilateral pendular nystagmus  Utilization of simple tools in the office  Non verbal, non coorperative  Treatment  Simple vision therapy activities including visual vestibular input  What can we do?  Difficult population poses challenges (non verbal,  Optimize visual acuity, treat ET if present non cooperative) but there are always  Visual vestibular therapy possibilities in care and treatment

 Nystagmus control with goal to improve visual acuity and sustained attention  After image transfer with near and far visual motor activities

REFERENCES QUESTIONS

 Abel LA. Infantile nystagmus: current concepts in diagnosis and management. Clin Exp Optom. 2006 Mar;89(2):57-65. Review.  Gottlob I, Proudlock FA. Aetiology of infantile nystagmus. Curr Opin Neurol. 2014 Feb;27(1):83-91. doi: 10  Harris C, Berry D. A developmental model of infantile nystagmus. Semin Ophthalmol. 2006 Apr-Jun;21(2):63-9. Review.  Lee AG, Brazis PW. Localizing forms of nystagmus: symptoms, diagnosis, and treatment. Curr Neurol Neurosci Rep. 2006 Sep;6(5):414-20. Review.  Leung V, Wick B, Bedell HE. Multifaceted treatment of congenital nystagmus: a report of 6 cases. Optom Vis Sci. 1996 Feb;73(2):114-24. Review.  Papageorgiou E, McLean RJ, Gottlob I. Nystagmus in childhood. Pediatr Neonatol. 2014 Oct;55(5):341-51. doi: 10.1016/j.pedneo.2014.02.007. Epub 2014 Jul 31.  Sarvananthan N, Surendran M, Roberts EO, Jain S, Thomas S, Shah N, Proudlock FA, Thompson JR, McLean RJ, Degg C, Woodruff G, Gottlob I. The prevalence of nystagmus: the Leicestershire nystagmus survey. Invest Ophthalmol Vis Sci. 2009 Nov;50(11):5201-6. doi: 10.1167/iovs.09-3486. Epub 2009 May 20.  Thurtell MJ, Leigh RJ. Treatment of nystagmus. Curr Treat Options Neurol. 2012 Feb;14(1):60-72.

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Cystoid Macular Case History Edema: A Case Report • 89 year-old Caucasian male, JF and Review • CC: No visual complaints, but notes that OD sees better than OS. Reports LEE outside VA 6-8 months ago, when doctor recommended YAG laser. Truyet Tran, OD • POHx: Cataract surgery OU ~2011 VA Portland Health Care System • PMHx: Hypertension, hyperlipidemia, coronary artery disease, CVA 2014 Primary Care Optometry Resident • Medications: atorvastatin, clopidogrel, tamsulosin, aspirin 325mg, Tylenol pm

Entering Tests Posterior Segment Exam

• Lens: PCIOL with 1+ PCO OD, OS • Best corrected visual acuities: • OD: 20/30 • Optic disc: 0.45r with distinct rims OD, OS • OS: 20/25- • Macula: • Pinhole acuity potential: • OD: Intermediate and large drusen with pigment clumping, no SRF/hemorrhage/exudate; • OD: 20/30 mild CME • OS: Intermediate and large drusen with pigment clumping, • OS: 20/20- no SRF/hemorrhage/exudate, flat with no CME • No defects on Amsler grid OD, OS • Posterior pole & periphery: • Preliminary tests normal • No retinal holes, breaks, or tears OU • OS: Flame-shaped hemorrhage superior arcade

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Fundus Photo OD Fundus Photo OS

Macular OCT Assessment

• Cystoid macular edema (CME) OD • DDx: s/p CE/IOL 2011 vs old BRVO vs CNV • Non-exudative age-related (ARMD) OU, AREDS 3 • Isolated flame heme OS • DDx: systemic hypertension vs clopidogrel use • Pseudophakia OU • Dry eye OU CMT: 430um

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Plan Macular OCT: 1 month follow-up

• Discussed treatment options and patient prefers non- invasive option • Initiate 0.5% ketorolac tromethamine ophthalmic solution qid OD and 1% prednisolone acetate ophthalmic suspension qid OD x 1 month

• RTC 1 month for follow-up or prn

• May consider IVFA in the future for diagnostic purposes, but not available at this visit

• Continue to monitor ARMD CMT: 317um

Plan Macular OCT: 3 month follow-up

• Decrease 0.5% ketorolac tromethamine ophthalmic solution to tid OD

• Begin 1% prednisolone acetate ophthalmic suspension taper: tid OD x 1 week, bid OD x 1 week, then qd OD until bottle runs out.

• RTC 2 months for follow-up or prn CMT: 286um

Plan: Monitor without treatment in 3 months or prn.

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Macular OCT Clinical Presentation

• Visual acuity ranges from 20/20-20/400 • Depends on foveal proximity and degree of macular thickening

• Slit lamp exam: • Loss of foveal depression, with radiating cystic spaces emanating from the macula • Honeycombed appearance with red-free filter • Loss of choroidal detail underlying macula

CMT: 430um CMT: 286um • Associated findings: Initial Presentation 3 Month F/U • Severe cases: vitreous cell, optic nerve swelling (chronic), lamellar hole

Diagnosis Diagnosis

• Fluorescein angiography shows pooling of dye in the • Optical coherence tomography (OCT): more sensitive macula: perifoveal capillary leakage in the early stage than FA for detection of CME. with a petalloid flower appearance in the late phase • OCT 95% vs FA 44% sensitivity for detection of definite CME • OCT is a more effective way to measure macular thickening and manage the effect of treatment

Early FA of CME Late FA of CME

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Pathophysiology Etiology

• Disruption of the blood retinal barrier leads to leakage of • Cataract surgery (Irvine-Gass syndrome) protein and water from plasma • Incidence: 0.1-2.35% cataract surgeries. • Intracellular and extracellular fluid accumulates within the • Onset: usually 4-16 weeks after surgery, peak: 4-6 weeks. macula • Factors that contribute to development of CME: type of cataract surgery, light toxicity, age, vitreous loss, integrity • Decreased pigment epithelium pump function may lead to of posterior capsule accumulation of fluid • Decreased incidence of CME associated with small-incision extra-capsular cataract phacoemulsification vs large-incision • Fluid accumulation disrupts cell function and retinal intra-capsular cataract extraction architecture • Muller cells, which act as metabolic pumps to keep macula dehydrated, are damaged which further reduces macular function

Etiology Etiology

• Diabetic retinopathy • Intraocular inflammation: uveitis • Chronic hyperglycemia leads to oxidative damage • Three fold increased risk of pseudophakic CME and inflammation • Traction: PVD or epiretinal membrane • Ensuing ischemia results in over-expression of • Inflammation is secondary to traction various growth factors, including VEGF • Hirokawa et al. (1985): eyes with complete vitreous detachment have fewer macular changes • Retinal vein occlusion • Hikichi and Trempe (1993): attached vitreous present in 78% • Cytokine release, hypoxia, increased hydrostatic pressure, of eyes with CME vs 22% of eyes without CME and vascular stasis all contribute to interstitial fluid • Medication toxicity: topical epinephrine, dipivefrin, or accumulation prostaglandin analogs

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Treatment Options Treatment Options

• Treat the underlying disorder • Intravitreal triamcinolone injection • Topical NSAIDs (eg., Voltaren or Acular qid, Nevanac tid, Bromday bid) and/or topical steroid (prednisolone acetate 1% qid for 1 month, slow taper). • Laser photocoagulation of perifoveal capillaries (in diabetes or retinal vein occlusion). If no response to topicals: • Periocular triamcinolone injection: reduced rate of • Vitrectomy or YAG vitreolysis to alleviate vitreomacular endophthalmitis compared to intravitreal injection, but traction, also removes inflammatory mediators and duration of effect is shorter improves access of topical meds to posterior pole • Oral NSAIDs (indomethacin), oral steroids (prednisone), and/or oral CAIs (acetazolamide).

Treatment Options Reasons for Topical Therapy

• Intravitreal Anti-VEGF injection: VEGF increases • Ease of management vascular permeability by relaxing endothelial cell junctions • Less invasive • Effective treatment option • Risks: endophthalmitis, RD, hemorrhage, OHTN, cataract, hypotony • Cost • Modified treatment options: combining • High safety profile corticosteroids and anti-VEGF agents, switching • Oral carbonic anhydrase inhibitors contraindicated in anti-VEGF agents, increasing frequency of injections chronic renal impairment • Injections have more serious potential complications

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Melton, R and Thomas, R. Clinical Guide to Ophthalmic Drugs. Review of Optometry. 2013.

Melton, R and Thomas, R. Clinical Guide to Ophthalmic Drugs. Review of Optometry. 2013.

Topical Corticosteroids

• Effective because corticosteroids also act on lipoxygenase, which facilitates a greater anti-inflammatory effect

• Limitations: can cause IOP increase, cataract formation, corneal thinning, increased risk of infection through inhibition of immune response

Melton, R and Thomas, R. Clinical Guide to Ophthalmic Drugs. Review of Optometry. 2013. Prostaglandins increase vasodilation and permeability of blood aqueous barrier

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Mean Increase in IOP observed IOP Effects of Topical Steroids with Topical Corticosteroids in Steroid Responders • Early generation corticosteroids, such as dexamethasone and prednisolone are more likely to result in IOP increases

• Newer corticosteroids, such as rimexolone and loteprednol etabonate offer similar anti-inflammatory efficacy with less effect on IOP

• IOP will usually return to pretreatment levels within 1-3 weeks of discontinuation

• Risk factors for steroid-induced IOP elevation: longer axial length, POAG, glaucoma suspect, family history of glaucoma

• Study by Novack et al. found that 1.7% patients using loteprednol etabonate for > 28 days had IOP spike, as compared to 6.7% Pleyer, U, Ursell, PG, and Rama, P. Intraocular Pressure Effects of Common Topical Steroids for Post-Cataract Inflammation: Are patients on prednisolone acetate They All the Same? Ophthalmol Ther. 2013; 2: 55-72.

Topical NSAIDs Topical NSAIDs

• Study by Warren et al: monotherapy 0.1% nepafenac • Prospective study comparing topical diclofenac 0.1% for 12 weeks in 15 known steroid responders vs fluorometholone 0.1% (effectively a placebo) in • At 12 weeks, VA improved from 20/74 to 20/39. Retinal CME prophylaxis thickness reduced by 200 microns, with no effect on IOP • Angiographic CME present in 5.7% diclofenac treated • At 6 month follow-up, 64% maintained stable vision eyes vs 54.7% fluorometholone treated eyes • Benefit from NSAID is regardless of the etiology of the CME

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Topical NSAIDs Treating Chronic CME

• Corneal permeability studies show that nepafenac has • Trials by Flach et al. suggest topical ketorolac 0.5% superior corneal penetration relative to the other is effective, and treatment for 3 months provides longer lasting benefit than 2 months. NSAIDs and it also has a higher effective drug level in the posterior segment, resulting in reduced prostaglandin • Study by Warren et al. looked at adding topical synthesis NSAIDs to intravitreal corticosteroid and anti- VEGF injections for chronic CME: • Bromfenac has less perceived burning/stinging and • NSAID therapy seems to potentiate improvements easier bid dosing from intravitreal corticosteroids and anti-VEGF • Only nepafenac and bromfenac showed reduced retinal thickness at 12 weeks and 16 weeks. • Only nepafenac produced a sustained improvement in acuity: 19% improvement at 16 weeks

Prophylactic Treatment Prophylactic Treatment

• Review of studies published in Ophthalmology in 2014 compared efficacy of topical steroids with topical NSAIDs in preventing • Randomized comparison of topical ketorolac 0.4% plus pseudophakic CME corticosteroid vs corticosteroid alone showed significantly • Patients randomized to steroid treatment had significantly higher reduced rate of CME with combo treatment after prevalence of inflammation (n=931) and pseudophakic CME phacoemulsification. (25.3% vs 3.8%, n=521). No significant difference in VA. • No difference in visual outcomes. • No evidence of increased risk of adverse events with use of NSAIDs • Recommendation: NSAIDs should be used in combination • Previous studies found increased risk of corneal melts and impaired with standard corticosteroid for post-surgical therapy. Use of corneal wound healing in prolonged use of topical NSAIDs NSAIDs in peri-operative period seems to significantly improve • Diclofenac, ketorolac, and nepafenac all have similar efficacy. No surgical outcome. evidence to recommend one NSAID over another • No significant difference in inflammation or pseudophakic CME • Pre-and post-op ketorolac 0.4% vs steroid alone showed between strong and weak steroids significantly less retinal thickening and lower incidence of • Risk of pseudophakic CME and control of inflammation CME improved with NSAID initiated 1-3 days prior to surgery

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Thank You References

Barofsky, Jonathan. “Cystoid Macular Edema.” Retina Care Center, 2013. Web. 5 Oct. 2013. http://www.retinacarecenternj.com/services2.php#main

Burling-Phillips, L. “After Cataract Surgery: Watching for Cystoid Macular Edema.” EyeNet Magazine, 2007. Web. 2 Jun 2015. http://www.aao.org/publications/eyenet/200701/retina.cfm

Chaudhary, C, Bahadhur, H, and Gupta, N. Study of cystoid macular edema by optical coherent tomography following uneventful cataract surgery. Int Ophthalmol. 2014.

“Cystoid Macular Edema.” Handbook of Ocular Disease Management. Jobson Publishing, 2000- 2001. Web. 5 Oct. 2013. http://cms.revoptom.com/handbook/oct02_sec5_1.htm

Ehlers, Justis and Chirag Shah. The Wills Eye Manual. Baltimore: Lippincott Williams and Wilkins, 2008. Print.

Friedman, Neil and Peter Kaiser. The Massachusetts Eye and Ear Infirmary. Elsevier, 2009. Print.

Jampol, LM, Bressler, NM, and Glassman, AR. Revolution to a New Standard Treatment of Diabetic Macular Edema. JAMA. 2014; 22: 2269-2270.

References References

Kessel, L, Tendal, B, Jorgensen, KJ, et. al. Post-catarct Prevention of Inflammation and Macular Edema by Steroid and Nonsteroidal Anti-inflammatory Eye Drops. Ophthalmology. 2014; 121: 1915-1924. Ouyang, Yanling et al. “Detection of Cystoid Macular Edema with Three-Dimensional Optical Coherence Tomography versus Fluorescein Angiography.” Investigative Ophthalmology and Visual Science: 51.10 (2010): 5213-5218. Web. 6 Oct. 2013. Levitz, L, Reich, J, Roberts, TV, et. al. Incidence of cystoid macualr edema: Femtosecond laser-assisted cataract surgery versus manual cataract surgery. J Cataract Refract Surg. 2015; 41: 683-686. Park, S, Lim, LT, and Gavin, MP. Topical Steroidal and Nonsteroidal Antiinflammatory Drugs for the Treatment of Cystoid Macular Edemea in Retinitis Pigmentosa. Retinal Cases & Brief Reports. 2013; 7: 134-136. Lobo, C. Pseudophakic Cystoid Macular Edema. Ophthalmologica.2012; 227: 61-67. Pleyer, U, Ursell, PG, and Rama, P. Intraocular Pressure Effects of Common Topical Steroids for Post-Cataract Inflammation: Are They All the Same? Ophthalmol Ther. 2013; 2: 55-72. Martin, DF and Maguire, MG. Treatment Choice for Diabetic Macular Edema. New England Journal of Medicine. 2015; 372: 1260-1261. Quintana, NE, Allocco, AR, Ponce, JA, et. al. Non steroidal anti-inflammatory drugs in the prevention of cystoid macular edema after uneventful cataract surgery. Clinical Ophthalmology. 2014; 8: 1209-1212. Munk, RM, Sacu, S, Huf, W, et. al. Differential Diagnosis of Macular Edema of Different Pathyophysiologic Origins by Spectral Domain Optical Coherence Tomography. Retina. 2014; 34: Rho, D. S. et al. “Bromfenac 0.09% versus diclofenac sodium 0.1% versus ketorolac tromethamine 0.5% in the treatment 2218-2232. of acute pseudophakic cystoid macular edema.” April 30–May 4, 2006; Fort Lauderdale, Fla.

Nehmad, L. Late Onset Cystoid Macular Oedema Presents as a Diagnostic Challenge. Clinical and Roth, Daniel et al. “Nonpseudophakic Cystoid Macular Edema.” Medscape, 2012. Web. 6 Oct. 2013. Experimental Optometry. 2014; 97: 459-462 http://emedicine.medscape.com/article/1225735-overview

Rotsos TG, Moschos MM. “Cystoid macular edema.” Journal of Clinical Ophthalmology. 2008; 2(4): 919–930. Ober, Michael et al. “Management Options for Macular Edema.” Review of Ophthalmology, 2005. Web. 2 Jun. 2015. http://www.revophth.com/content/d/retinal_insider/i/1310/c/25220

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References

Russo, A, Costagliola, C, Delcassi, L, et. al. Topical Nonsteroidal Anti-Inflammatory Drugs for Macular Edema. Mediators of Inflamation. 2013.

Sahoo, S, Barua, A, Myint, KT, et. al. Topical non-steroidal anti-inflammatory agents for diabetic cystoid macular oedema (Review). The Cochrane Collaboration. 2015.

Sivaprasad, S, Bunce C, and Crosby-Nwaobi R. Non-steroidal anti-inflamamtory agents for treating cystoid macular oedema following cataract surgery (Review). The Cochrane Collaboration. 2012.

Tzelikis, PF, Vieira, M, Hida, WT, et. al. Comparison of ketorolac 0.4% and nepafenac 0.1% for the prevention of cystoid macular oedema after phacoemulsification: prospective placebo-controlled randomised study. Br J Ophthalmol. 2014; 0: 1-5.

Virgili, G, Parravano, M, Menchini, F, et. al. Antiangiogenic therapy with anti-vascular endothelial growth factor modalities for diabetic macular oedema (Review). The Cochrane Collaboration. 2012.

Warren, KA, Bahrani, H, Fox, JE. NSAIDS in Combination Therapy for the Treatment of Chronic Pseudophakic Cystoid Macular Edema. Retina. 2010; 30: 260-266.

Warren, KA and Fox, JE. Topical Nepafenac as an Alternate Treatment for Cystoid Macular Edema in Steroid Responsive Patients. Retina. 2008; 28: 1427-1434.

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Exogenous and endogenous corticosteroids and their link to Getting serious with retinopathy Central Serous Chorioretinopathy

Gleb Sukhovolskiy, O.D. Jonathan M. Wainwright Memorial VAMC

Objectives Patient JM –70 y.o. male • CC: Seeing a crescent shape in right eye for 10 days. • By the end of the presentation, attendees will be able to • Uncorrected VA: 20/20-2 OD and 20/25-2 OS o Recognize the association between corticosteroids and • PERRL (-)APD central serous chorioretinopathy • FTFC OD and OS o Identify factors that aid corticosteroid absorption • IOP: 12/10 mmHg o Recognize the role of hypothalamus-pituitary-adrenal axis • Lens: clear PCIOL OU, slight sup displacement OD and sympathetic nervous system in stress response • Vitreous: PVD OU o Recognize the role of elevated plasma cortisol in CSC • C/D: 0.35r OD and 0.40r OS o Discuss the role of choroid and RPE in the development of • Macula: o OD: small (<1/4DD) area of elevation centrally OD; CSC o OS: larger area of elevation with pigment changes centrally; • Vessels: normal • Periphery: intact

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Differential diagnoses5,6

• DME • ARMD • BRVO • CRVO • Hypotony maculopathy • Retinal vasculitis • Retinal macroaneurysm • Ocular histoplasmosis • Polypoidal choroidal vasculopathy • Optic nerve pit • Idiopathic uveal effusion syndrome Bilateral Central Serous Chorioretinopathy. • Posterior scleritis

CSC overview CSC risk factors • Fourth most common retinopathy1 • Pregnancy7 • After ARMD, diabetic retinopathy, vein occlusions • Anatomy • Psychological stress8 o Serous retinal detachment 10 o Fluid leakage at the level of RPE • HTN • Healthy males • Type A personality11 o 9.9 in 100,000 men and 1.7 in 100,000 women3 10 • Symptoms • Psychopharmacologic medication use o Asymptomatic • Corticosteroid use9 o Decreased visual acuity o Metamorphopsia http://www.premierretina.com/images/csr2.jpg o Positive scotoma • Acute vs. chronic form • Treatment o Observation o Laser photocoagulation4 o Photodynamic therapy with verteporfin37

www.retinavitreouscenter.net/wbcntntprd/wp‐content/ uploads/Central‐Serous‐Retinopathy_CSRFA‐300x300.jpg

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Medications 2‐month follow‐up • Adalimumab inj pen kit • Albuterol/Ipratropium inhaler • CC: visual phenomenon still present, but decreasing • Ammonium Lactate cream in intensity. Still taking steroid creams and inhaler. • Balsalazide Disodium • Betamethasone Valerate 0.1% cream • VA: 20/20 OD and OS • Clobetasol Propionate 0.05% ointment • PERRL (-)APD • Hydroxyzine Pamoate • Mometasone Furoate 220mcg inhaler • IOP: 14/13 mmHg • Omeprazole • Polyethylene Glycol • Posterior segment same OU • Pravastatin o Except flat macular appearance OU • Sodium Fluoride oral cream • Triamcinolone 0.1% cream • Venlafaxine • Aspirin 81mg • Nefadozone

Glucocorticoids and CSC • No data to estimate prevalence of CSC in patients on treatment with glucocorticoids • About 3.3%-9.1% of CSC patients were on steroids10,26 • Over 200 cases reported in literature of CSCR during glucocorticoid therapy:9 o Oral routes o Intravenous o Intramuscular o Epidural o Inhaled o Intranasal o Topical skin applications o Combination of two modes • Intrestingly ocular steroids not so much (topical or intravitreal)

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Steroid‐associated CSC CSC from topical dermal steroids • Older age9 • More bilateral and chronic • 43 yo F from mometasone furoate 1% cream for lichen planus in arms – did not o Bilaterality in woman 23% vs 11% 27 discontinue, focal laser tx at 7 months without complete resolution, but 13 o 33% in exogenous vs. 20% in all 28,29 improved acuity • 47 yo F used steroid cream (unknown) for psoriasis (last administration • Male:Female ratio more equal coincided with start of symptoms), resolved at 9 months even with intermittent o 3:1 vs 8:19 continued steroid cream use 14 o Woman who develop CSCR are more likely than men to use steroids10,26,27 • 25 yo M used calcipotriene 0.005% cream for psoriasis for 16 months, • Wide range of dosages and treatment durations discontinued, condition resolved in 3-4 months 12 o 10-15mg per day to 1 g IV per day 9 • 32 yo M used 1% hydrocortisone acetate cream for facial seborrheic dermatitis 15 o Few days to few years • 37 yo M using diflucortolone valerate 0.1% cream for pityriasis versicolor 15 • Other considerations o Diseases treated with corticosteroids o Catecholamines 23,24 o Testosterone 25

Class 1 (Super‐potent) 13

• Clobetasone propionate cream, ointment 0.05% • Betamethasone dipropionate cream, ointment 0.05% (optimized vehicle) Clobetasone propionate ointment 0.05% • Diflorasone diacetate ointment 0.05% (optimized vehicle)

Class 2 (Potent)

• Amcinonide ointment 0.1% Main factors in drug absorption • Betamethasone dipropionate cream, ointment 0.05% (optimized vehicle) • Mometasone furoate intment 0.1% • Diflorasone diacetate ointment 0.05% • Halcinonide cream 0.1% • Fluocinonide gel, cream, ointment 0.05% • Diflorasone diacetate ointment 0.05% • Strength/potency of steroid • Desoximetasone cream, gel, ointment 0.25% Class 3 (Potent)

• Triamcinolone acetonide ointment 0.1% • Length/frequency of application •Fluticasone propionate ointment 0.005% • Amcinonide cream, lotion 0.1% • Betamethasone dipropionate cream 0.05% •Diflorasone diacetate cream 0.05% • Nature of skin problem • Halcinonide ointment 0.1% • Fluocinonide cream 0.05% •Diflorasone diacetate cream 0.05% • Site treated13 • Betamethasone valerate ointment 0.1% Class 4 (mid‐strength) o Forearms: 1% • Flurandrenolide ointment 0.05% • Mometasone furoate cream 0.1% • Triamcinolone acetonide cream 0.1% Triamcinolone acetonide cream 0.1% o Armpits: 4% • Fluocinolone acetonide ointment 0.025% • Hydrocortisone valerate ointment 0.2%

o Face: 7% Class 5 (mid‐strength)

• Flurandrenolide cream 0.05% o and genitalia: 30% •Fluticasone propionate cream 0.05% • Betamethasone dipropionate lotion 0.05% • Triamcinolone acetonide lotion 0.1% o Palm: 0.1% • Hydrocortisone butyrate cream 0.1% • Fluocinolone acetonide cream 0.025% o Sole: 0.05% • Betamethasone valerate cream 0.01% Betamethasone valerate 0.01% • Hydrocortisone valerate cream 0.2%

Class 6 (mild)

• Aclometasone dipropionate cream, ointment 0.05% • Triamcinolone acetonide cream 0.1% •Desonidecream 0.05% • Fluocinolone acetonide solution, cream 0.01% •Desonidecream 0.05% • Betamethasone valerate lotion 0.1%

Class 7 (mild)

• Hydrocortisone, dexamethasone, flumethasone, prednisolone, methylprednisolone

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CSC from inhaled/intranasal corticosteroids

• 43 yo M using beclomethasone dipropionate inhaler for bronchial asthma for years, did not discontinue, resolved in 5 months • 31 yo M using triamcinolone acetonide inhaler for excercise-induced asthma for years, did not discontinue, resolved in 7 months • 45 yo F using fluticasone propionate 0.05% nasal spray for bronchitis for 6 days, discontinued spray, reduced, but still present detachment at 6 months • 47 yo F using beclomethasone dipropionate inhaler for 6 months for chronic bronchitis, continued use, at 4 months detachment still there, but diminished • 24 yo M using beclomethasone inhaler for allergic rhinitis for 1 month, discontinued medication, resolved in 1 month • 41 yo M using beclomethasone dipropionate nasal spray for 4 weeks for allergic rhinitis, did not discontinue, did not return for follow-up • 48yo F using fluticasone propionate nasal spray for allergic rhinitis for 1 week, almost completely resolved in 4 weeks with discontinuation of med • 40 yo F using fluticasone inhaler for bronchospasm post mycoplasma pneumonia for 4 months, resolved over the next several weeks

ʺHPA Axis Diagram (Brian M Sweis 2012)ʺ by BrianMSweis

HPA axis suppression with Topical corticosteroid absorption inhaled corticosteroids • Plasma cortisol studies in patients with psoriasis 17 • Statistically significant plasma cortisol suppression21 o Morning plasma cortisol measured Healthy adults o 14 days o 24-hour plasma cortisol o 30 patients o Even after single administration o No difference between pre, post and during treatment measurements • Meta-analysis of 31studies22 • Cushing’s syndrome in several cases o Adults with asthma Percentage with HPA 16 Role of negative feedback • Several cases of prolonged HPA axis suppression o suppression o High doses o Statistically significant suppression o Misuse of drug • 17.92% of low dose users Low o Most cases clinically insignificant o Mometasone furoate 200-400mcg • 26.55% of medium dose users Medium • 36.31% of high dose users High o What does statistical significance mean? 0.00% 50.00% http://www.hormone.org/~/media/Hormone/Images/Questions%20and%20Answers/Pituitary/Cushings.jpg

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Patient LS –39 y.o. female • CC: Can’t see soccer ball when watching games on TV. • History of burned left eyeball with a curling iron at 12 yo • VA: 20/20 OD and OS with strain • PERRL (-)APD; full motilities OU; visual fields FTFC OU • Manifest refraction: +0.25 sph OU • Unremarkable anterior segment • IOP: 10/09 with Tonopen • Lens: Clear OU • Vitreous: Clear OU • C/D: 0.4r OU; temporal pallor OU • Macula: 1 DD area of elevation OD, with hypopigmentation; OS: flat, dry (+)FLR • Vessels: normal OU • Periphery: intact OU

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Pertinent Medical History Diagnosis

• H/o attempted suicide 2 weeks prior • 1. Idiopathic central serous retinopathy, OD. Patient • Anxiety unaware of onset. • Insomnia • 2. Possible mild nutritional optic neuropathy OU. • History of alcoholism • 3. Presbyopia OU. • Anorexia • Bulimia Nervosa • Major depression • 1. Patient education. Monitor in 2 months. • Eating disorder • 2. Ordered serum B-12. Thorough education on nutrition, alcohol consumption. Consider VF testing. • 3. +1.25 sph reading glasses recommended.

The role of stress • Type A behavior 11 CC: Can’t see soccer CC: No changes, CC: No changes, o Competetive drive ball when watching continued stress, continued stress, o of ugency games on TV. improved diet. improved diet. o Aggressive nature o Hostile temperament VA: 20/20 OD and OS VA: 20/20-2 OD and OS VA: 20/25 OD and OS • Type A vs. Type B PERRL (-)APD PERRL (-)APD PERRL (-)APD o 60% of CSC patients have Type A behavior IOP: 13/15 with Tono IOP: 18/17 with Tono o Patient with CSC is 3.4x more likely to be Type A than Type B IOP: 10/09 with Tono • People with Type A show increased sympathetic activity in Posterior Pole: 1 DD area Posterior pole: 1DD Posterior pole: ½ DD response to challenging situations, as compared to Type B of elevation OD, with area of elevation OD in area of elevation OD in o Skin temperature 41 44 hypopigmentation; OS: the macular region; the macular region; o Muscle vasodilation Clear OS Clear OS o Pupillary dilation 45 flat, dry (+)FLR o Pulse rate 41 o Blood pressure 42 o Plasma catecholamines 43,45 o Plasma cortisol 44 08/05/2014 10/28/2014 03/19/2015 • Type A students produced 40x more cortisol and 4x more epinephrine than Type B students 46

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SENSORY INPUT 30 Prefrontal cortex47 Stress PREFRONTAL CORTEX • Does not fully develop until 25 y.o. • No neural element in stress HIPPOCAMPUS Sympathetic response CRH release AMYGDALA Nervous System • No CSCR in kids

HYPOTHALAMUS CRH Norepinephrine HPA axis PITUITARY GLAND release activation LOCUS COERULUS ADRENAL CORTEX

Increased glucose, Noradrenaline Increased arousal, RPE/BM interface heart rate, blood vigilance, anxiety pressure CSCR

30 Adaptation during stress Chronicity of stress response Behavioral Adaptation • Stress response is meant to be of limited duration •Acute facilitation of adaptive and inhibition of non‐adaptive neural pathways Anti-anablic, catabolic, immunosuppressive effects •Increased arousal, alertness o •Increased cognition, vigilance, and focused attention • One-time CSC in over 50% •Suppression of feeding behavior o Adaptation by anticipatory response 47 •Suppression of reproductive behavior o Learning predictive cues •Containment of stress response o Increased glucocorticoids after acute stress, but decreased after chronic 48,49 Physical Adaptation intermittent stress •Oxygen and nutrients directed to the CNS and stressed body site • Chronic stress response results in severe chronic •Altered cardiovascular tone, increased blood pressure and heart rate disease 30 •Increased respiratory rate o Failure of adequate counterregulation •Increased gluconeogenesis and lipolysis o Limited adaptation becomes prolonged maladaptation •Detoxification from toxic products •Inhibition of growth and reproductive systems •Containment of stress response •Containment of inflammatory/immune response

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Maladaptive stress response. Disorders associated with dysregulation of

AKA ‐ Melancholic depression. the stress system 30

30 Increased Stress System Activity Decreased Stress System Activity

• Severe chronic disease •Atypical depression •Anorexia nervosa • Cushing’s syndrome Arousal Anxiety • Melancholic depression • Seasonal depression Vigilance Hypervigilance, insomnia •Panic disorder •Chronic fatigue syndrome • Obsessive‐compulsive disorder • Hypothyroidism Cognition Focus on depressive ideas •Chronic active alcoholism •Obesity Assertiveness Excessive cautiousness • Alcohol and narcotic withdrawal • Posttraumatic stress disorder •Chronic excessive exercise • Nicotine withdrawal Decreased emphasis on Anorexia, decreased • Malnutrition • Vulnerability to inflammatory feeding and reproduction libido • Hyperthyroidism disease •Premenstrual tension syndrome • Vulnerability to addiction

Combining the two Role of the RPE • Defect in RPE Increased 38 Exogenous • Focal defects promote flow into choroid cortisol from corticosteroid • Steroids can modify electrophysiological stress absorption parameters, influencing fluid transport 32 response • Steroids enhance blood-brain barrier by strengthening tight junctions 33 • Perhaps, increased tissue hydrostatic pressure in the CSC choroid along with focal loss of RPE polarity can result in fluid penetration into subretinal space.

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Role of the choroid Final thoughts… • Choroidal hyperpermeability • Choroidal thickness measurements • “…disorder is not caused by a solitary etiologic o Thicker in eyes with CSC 35 factor producing a specific constellation of macular o Thicker in fellow eyes if choroidal hyperpermeability is present 36 manifestations. Rather, its pathogenesis is more likely • Stasis, ischemia, inflammation related to the interrelationship between finely o Why do steroids not cure CSC? balanced components of a complex • Tissue-specific factors? 47 biopsychological system involving a person’s • Corticosteroids and the regulation of blood flow genetic endowment, environment, and behavioral o Inhibition of nitric oxide production 39,40 pattern.”11 o Hypertension/choroidal blood flow elevation 52 o Hypercoagubility and augmented platelet aggregation 50 o Cadherin 5 and genetic variation 51

1. Wang M, Munch IC, Hasler PW, Prunte C, Larsen M. Central serous chorioretinopathy. Acta Ophthalmol 2008; 86:126-45. 2. Nicholson B, Noble J, Forooghian F, Meyerle C. Central Serous Chorioretinopathy: Update on Pathophysiology and Treatment. Surv Opthalmol 2013; 58:103-126. 3. Kizmann AS, Pulido JS, Diehl NN, Hodge DO, Burke JP. The incidence of central serous chorioretinopathy in Olmsted County, Minnesota, 1980-2002. Ophthalmology 2008; 115:169-173. 4. Leaver P, Williams C. Argon laser photocoagulation in the treatment of central serous retinopathy. Br J Ophthalmol 1979; 63:674-677. 5. Turgut et al. The causes of serous macular detachment excluding central serous retinopathy. Clinical Optometry 2010; 2:51-54. 6. Shuler RK, Mruthyunjaya P. Diagnosing and managing central serous retinopathy. American Academy of Ophthalmology website 2006. http://www.aao.org/publications/eyenet/200602/pearls.cfm 7. Haimovici R, Rumelt S, Melby J. Endocrine abnormalities in patients with central serous chorioretinopathy: a case-control study. Ophthalmology 2004; 11:224-9. 8. Gelber GS, Schatz H. Loss of vision due to central serous chorioretinopathy following psychological stress. Am J Psychiatry 1987; 144:46-50. 9. Bouzas EA, Karadimas P, Pournaras CJ. Central serous chorioretinopathy and glucocorticoids. Surv Ophthalmol 2002; 47:431-448. 10. Tittl et al. Systemic findings associated with central serous chorioretinopathy. Am J Ophthalmol 1999; 128:63-68. 11. Yannuzzi LA. Type A behavior and central serous chorioretinopathy. Tr Am Opth Soc 1986; 84:799-845. 12. Ezra N, Taban M, Behroozan D. Central serous chorioretinopathy associated with topical corticosteroids in a patient with psoriasis. J Drugs Dermatol 2011; 10(8):918-921. 13. Fernandez CF, Mendoza AJ, Arevalo JF. Central serous chorioretinopathy associated with topical dermal corticosteroids. Retina, the Journal of Retinal and Vitreous Diseases 2004; 24(3):471-474. 14. Mirza RG, Gill M. Central serous chorioretinopathy associated with unusual routes of steroid administration. Retinal Cases & Brief Reports 2009; 3:99-101. 15. Karadimas P, Kapetanios A, Bouzas E. Central serous chorioretinopathy after local application of glucocorticoids for skin disorders. Arch Ophthalmol 2004; 122:784-786. 16. Dhar S, Seth, J, Parikh D. Systemic side-effects of topical corticosteroids. Indian J Dermatol 2014; 59(5):460-464. 17. Tomasini C, Castiglioni G. Plasma cortisol studies with 0.05% halometasone cream and ointment in patients with psoriasis. J Int Med Res 1983; 11:38-42. 18. Haimovici R, Gragoudas ES, Duker JS, Sjaarda RN, Eliott D. Central serous chorioretinopathy associated with inhaled or intranasal corticosteroids. Ophthalmology 1997; 104:1653-1660. 19. Fardin B, Weissgold DJ. Central serous chorioretinopathy after inhaled steroid use for post-mycoplasma bronchospasm. Br J Ophthalmol 2002; 86(9):1065-1066. 20. Kleinberger AJ, Patel C, Lieberman RM, Malkin BD. Bilateral central serous chorioretinopathy caused by intranasal steroids: a case report and review of the literature. Laryngoscope 2011; 121:2034-2037. 21. Brus R. Effects of high-dose inhaled corticosteroids on plasma cortisol concentrations in healthy adults. Arch Intern Med 1999; 159:1903-1908. 22. Wlodarczyk JH, Gibson PG, Caeser M. Impact of inhaled corticosteroids on cortisol suppression in adults with asthma: a quantitative review. Ann Allergy Asthma Immunol 2008; 100:23-30. 23. Haimovici R, Rumelt S, Melby J. Endocrine abnormalities in patients with central serous chorioretinopathy. Ophthalmology 2003; 110:698- 703. 24. Sun J, Tan J, Wang Z, Yang H, Zhu X, Li L. Effects of catecholamine on central serous chorioretinopathy. Journal of Huazhong University of Science and Technology 2003; 23(3):313-316. 25. Zumoff B, Rosenfeld RS, Friedman M, Byers S, Rosenman RH, Hellman L. Elevated daytime urinary excretion of testosterone glucoronide in men with the type A behavior pattern. Psychosomatic Medicine 1984; 46(3):223-225. 26. Wakakura M, Suzuki H. Urinary excretion of catecholamines in central serous chorioretinopathy. Jpn J Clin Ophthalmol 1979; 33:1237-40. 27. Quillen DA, Gass DM, Brod Rd, et al. Central serous chorioretinopathy in women. Opthalmology 1996; 103:72-9.

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 32 yowm  Presented to clinic in 2009 with c/o: . OS blur x 3 months, progressively worsening By: Shannon Currier, OD ▪ (+) light sensitivity VA Portland Health Care System Portland, Oregon ▪ (-) pain

 Personal Ocular History . Previously emmetropic: 20/20 OU (sc)

 Traumatic Brain Injury  Medication  Visual Acuity (sc)  Dry . 4 combat tours with repeated . Citalopram . OD: 20/15-1 . OD: +0.25 +0.50 x 090 exposure to explosions (IEDs, . Vicodin mortars). Closest proximity noted . OS: 20/80+2 PH: . OS: +4.25 DS . Indomethacin to be ~5-10 meters. 20/60+2 . 3-4 of the incidents resulted in . Trazodone . *Letters on right side altered consciousness.  Manifest Refraction:  NKDA of chart are easier to . OD: +0.50 DS 20/15 read  Migraine Headaches with . OS: +4.25 DS 20/25 aura . 3-4 times/week  Wet Retinoscopy: . Vicodin helps . OD: +0.75D  Insomnia . OS: +4.00 +0.75 x 045

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 Pupils: (-)APD  Tonometry: at 14:57  Optic Disc: severe oblique insertion . OD: 3.5 2.5mm . OD: 11 mmHg . C/D Ratio: OD: 0.35r OS: 0.35r . OS: 5.0 4.0mm . OS: 12 mmHg  Maculae: . OD: (+)FLR; flat, uniform pigment  EOMS  Anterior Segment: . OS: horizontal choroidal folds & retinal traction . Full/no restrictions OU . Lids: wnl OU  Posterior Pole: . Cornea: clear OU . OS: macular traction with choroidal folds extending  Confrontation VF . Conjunctiva: W&Q OU nasally past ONH ~ 6DD x 4.5DD. . FTFC OU . Anterior Chamber: D&Q OU (-)ERM . Iris: wnl OU  Peripheral Retina:  Cover Test (sc) . Lens: clear OU . OU: mild vitreous condensation inferiorly . Orthophoric . No retinal holes, breaks or detachments with scleral depression OU

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 Macular Cube OCT:  Exophthalmometry  B-Scan Ultrasonography . OD: normal foveal . OD: 21mm . OD: No abnormalities contour, no SRF/IRF; central macular . OS: 21mm . OS: Flattening of posterior thickness: 231 um globe with NO visible evidence . Base: 103mm . OS: increased retinal of retrobulbar mass thickness choroidal folds, irregular  FDT 20-5 Screener contours with vertical

. Reliable OU cross section, extends from retinal layers to . OD: No VF defects RPE layers; central . OS: 1 defect inferior nasal macular thickness: (p<2%) 276 um

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 MRI (face and orbits, with and without contrast): . “Normal appearance of the orbits and globes bilaterally. No mass identified. Minimal paranasal sinus disease stable from prior CT. Enhancement of OS.”

 CT (orbit, sella, fossa with & without contrast) 1mm cuts: . “Orbits & globes are unremarkable. There is no retrobulbar mass lesion. Osseous structures intact. Soft tissues are without focal abnormality.”

 Definition:  More commonly seen:  Signs & Symptoms: . “Undulations of the inner choroid, Bruch’s membrane and RPE that develop secondary to any intra- or extraocular process that . Males (~2:1) . Visual blur 2,7 induces compressive forces sufficient to buckle these tissues” . Caucasians . Hyperopic shift

 Seen as alternating dark and light bands with . Metamorphopsia  Commonly associated . Asymptomatic

 Represent a CLINICAL SIGN rather than a specific with systemic disease diagnosis: . Inflammatory . Diplopia* . Prompt testing is required to find a cause and rule-out more . Neoplastic serious etiology . Proptosis* . Idiopathic chorioretinal folds are a diagnosis of EXCLUSION . Infiltrative

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 Linear/circumlinear  Distribution wrinkles that extend . More common temporal to through the optic disc . Typically see 2-20 parallel posterior pole lines in posterior pole . Rarely extend beyond the equator  . Bilateral or unilateral* Orientation . Broaden with time . Parallel linear . Easily observed with: ▪ Horizontal > >vertical ▪ Autofluorescence . Radial ▪ Fluorescein angiography . Concentric . Primary vs. Secondary* . Random

 Retinal Folds: involve only neural retina; the RPE, THIN RPE Other Bruch’s membrane and choroid remain unaffected  Tumor  Idiopathic  Hypotony  Hyperopia . More common  Inflammation/Idiopathic  CSCR . Superficial with narrow spacing  Neovascular Membrane  AMD . Normal fluorescein angiogram pattern  Trauma (orbital fracture) . Examples:  Retrobulbar mass  Orbital Cellulitis ▪ Traction vitreoretinal forces:  Papilledema  Chorioretinal scars ▪ Epiretinal membrane  Extraocular Hardware  Uveal effusion ▪ Diabetic fibrovascular membranes (scleral buckle) syndrome ▪ Proliferative vitreoretinopathy secondary to retinal detachment ▪ Patton’s Folds

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 Tumor  Retrobulbar Mass . Choroidal tumor . Orbital tumor  Hypotony  Papilledema  Inflammatory/Infiltrative . Intracranial . Posterior scleritis hypertension . Uveitis  Extraocular . Thyroid eye disease Hardware  Neovascular Membrane . Scleral Buckle

1. External mechanical compression and/or shrinkage of the eye wall leads to What causes the choroid to fold? deformation of sclera and choroid . Stress/Strain Relationship . Orbital tumors • Scleral tissue is quite rigid, therefore any deformation (shrinkage/thickening) of the scleral causes the more elastic . Choroidal tumors adjacent choroid to “bunch up” or fold. . Papilledema

. Scleral buckle • “A column of human choroid/Bruch’s membrane/ RPE are expected to buckle at 1/50th of the stress required to buckle a typical column of sclera”

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2. Shear-induced wrinkling: tangential force 3. Imbalance between contractile forces of created by contraction of neighboring the outer coats of the eye wall (sclera vs. tissue choroid) . Choroidal neovascularization with secondary . Hypotony & Uveitis: decreased intraocular contraction pressure leads to choroidal thickening while the . Chorioretinal scars scleral thickness remains constant . Posterior scleritis

 Orbital tumors  Choroidal  Extremely helpful in identification of choroidal . Intra-conal: radiating neovascularization with folds away from the disc secondary contraction & . Extra-conal: concentric chorioretinal scars . Shows alternating bands of hyper- and with convex side toward . Radial toward center of hypofluorescence in arterial and early venous phase optic disc contraction .  Choroidal tumors  Hypotony & Uveitis This pattern typically fades in the later recirculation . Concentric along tumor . Random/Multidirectional phase edge pattern  Scleral buckle  Papilledema . Multiple linear folds . Circumpapillary  Presence of leakage helps detect any associated perpendicular to plane of the buckle choroidal neovascularization

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 Hyperfluorescent  A scan: biometry:  Useful Diagnostic Tool: (peaks) = less . Axial length . R/o orbital & choroidal compressed RPE; fewer . Retinochoroid layer tumors melanocytes to filter thickness . Determine underlying choroidal fluorescence etiology  B scan: topography: ▪ Shows scleral shortening  Hypofluorescent ▪ Choroidal thickness: scleritis, . Posterior ocular wall trauma, hypotony (valleys) = compressed contour . Enlargement of RPE yields higher . Elevation of optic disc concentration of retrobulbar orbital . Retinochoroid layer structures: melanocytes that thickening effectively filter out the ▪ Optic nerve ▪ Extraocular muscles background choroidal ▪ Tenon’s capsule fluorescein

 Helps to:  Imaging of choroidal . R/o orbital tumors folds . Show flattening of . Bunching/folding of RPE globe  Helpful in determining etiology: . Show enlargement of optic nerve head . Choroidal thickening (scleritis) due to fluid ▪ Enhanced-depth OCT accumulation  Presence of subretinal fluid . CNVM

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 Chronic chorioretinal folds may result in unique maculopathy: • 2014 retrospective study at Emory University . 3 stages each with a specific angiographic appearance that looked at: . Gradual visual decline . Possible development of choroidal neovascularization • 57 affected eyes from 40 patients

• Goals:  Pathophysiology: . Loss of elasticity and increased fragility of Bruch’s 1. Review common chorioretinal fold etiologies membrane created by the long-term mechanical 2. Describe chorioretinal fold-related maculopathy stress of folding leads to fractures of Bruch’s membrane  choroidal neovascularization

 Based on fluorescein angiographic appearance:  Relatively few cases of stage 3 maculopathy . Stage 1: alternating bands of hyper- and hypo- with CNV were noted: fluorescence, no leakage . Stage 2: small areas of staining consistent with small . 10 eyes had stage 3 maculopathy breaks in Bruch's membrane ▪ 4 of these 10 eyes developed CNV . Stage 3: shows early hypofluorescence or delayed filling followed by late, poorly demarcated leaking  Anti-VEGF therapy (Avastin & Lucentis) hyperfluorescence and possible development of CNVM (similar to occult choroidal neovascularization) showed resolution of CNV but did NOT ▪ Late leakage of undetermined source – Macular improve visual acuity Photocoagulation Study

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 The 2014 case series by Olsen and associates showed that  Extensive imaging, ancillary testing and only 15% of cases were considered to have idiopathic complete systemic work-up may be folds. This decrease in number is likely secondary to improved diagnostic techniques necessary to determine cause  In 1983 Friberg proposed: “it is plausible that posterior scleritis may have previously occurred causing permanent  Treatment largely dependent upon thickening of posterior sclera with secondary flattening of underlying etiology the globe posteriorly.”

 Reports have shown an association of “idiopathic”  Careful monitoring for development of CNV choroidal folds with undiagnosed intracranial . OCT hypertension. . Other cases that have shown choroidal folds as the initial . FA finding (preceding papilledema) of elevated intracranial pressure

 Initial Assessment/Plan:  Choroidal folds are an important CLINICAL . Acquired hyperopia with idiopathic choroidal folds SIGN that require further testing and ▪ Released spectacle Rx with BCVA OS of 20/25, monitor in 6 months investigation to determine the underlying etiology  Final Assessment/Plan: . Idiopathic (hyperopia)    Orbital Tumors . Posterior Scleritis with associated choroidal folds ▪ Contact lens (RGP) fitting ▪ Oral corticosteroids & immunosuppressant  Careful monitoring for choroidal ▪ Corticosteroid injections neovascularization

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1. Olsen, Timothy W. "Chorioretinal Folds: Associated 5. Friberg, Thomas R., MD, and Arthur S. Grove, MD. Disorders and a Related Maculopathy." American Journal "Choroidal Folds and Refractive Errors Associated with of Ophthalmology 157.5 (2014): 1038-047. Orbital Tumors: An Analysis."Archives of 2. Friberg, Thomas R. "The Etiology of Choroidal Folds: A Ophthalmology 101 (1983): 598-603. Biomechanical Explanation." Graefe's Archive for Clinical 6. Atta, Hatem R., MD, FRCS, and Sandra F. Byrne. "The and Experimental Ophthalmology 227 (1989): 459-64. Findings of Standardized Echography for Choroidal 3. Jaworski, Andrew, James S. Wolffsohn, BSc, and Folds." Archives of Ophthalmology 106 (1988): 1234-241. Genevieve A. Napper, MSc. "Aetiology and Management 7. Uchihori, Hiroaki, Kei Nakai, and Yasushi Ikuno. of Choroidal Folds." Clinical and Experimental "Choroidal Observations in Posterior Scleritis Using High- Optometry 82.5 (1999): 169-76. penetration Optical Coherence 4. Del Priore, Lucian V., MD, PhD. "Stiffness of Retinal and Tomography." International Ophthalmology 34 (2014): Choroidal Tissue: A Surface Wrinkling Analysis of 937-43. Epiretinal Membranes and Choroidal Folds." American 8. Stimac, Gary K., Richard P. Mills, and Roger A. Dailey. "CT Journal of Ophthalmology 142 (2006): 435-40. of Acquired Hyperopia with Choroidal Folds." American Journal of Neuroradiology8 (1987): 1107-111.

9. Cassidy, Lorraine M., and Michael D. Sanders. "Choroidal Folds and Papilloedema." British Journal of Ophthalmology 83 (1999): 1139-143 10. Murdoch, David, FRANZCO, and Michael Merriman, FRANZCO. "Acquired Hyperopia with Choroidal Folds." Clinical and Experimental Ophthalmology 30 (2002): 292-94. 11. Gasperini, Julie, MD, Dean Elliot, MD, and E.T. Cunningham Jr., MD, PhD, MPH. "How to Recognize and Treat Chorioretinal Folds." Review of Ophthalmology 14 (2006): n. pag. 12. Sarraf, David, MD, and Steven Schwartz, MD. "Bilateral Choroidal Folds and Optic Neuropathy: A Variant of the Crowded Disk Syndrome?"Ophthalmology 110.5 (2003): 1047-1052.

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• Evaluation, diagnosis and treatment of patients with ocular motor cranial nerve palsies.

• By the end of the presentation, attendees will be able to: • describe the pathway of cranial nerves III, IV and VI Janice Pierce, OD • recognize the features of ocular motor cranial nerve palsies Primary Care and Ocular Disease • explain appropriate evaluation of ocular motor cranial nerve palsies VA Southern Oregon Rehabilitation Center and Clinics [email protected] • differentiate between palsies of the oculomotor, trochlear and abducens nerves • identify potential causes of ocular motor cranial nerve palsies • identify the location of ocular motor cranial nerve pathology

• 72 YOWM presented with sudden onset constant horizontal • POHx: diplopia that started on 11/25/14 • History of metal foreign bodies removed without complication • Difficulty opening right eye with intermittent headache while trying to • Choroidal nevus OD open it • S/P LPI OU • One incident of nausea without emesis • History of EOM palsy 15-18 years prior, resolved in about 2 months • Right eye is turned out • Normal MRI at time of palsy • Diplopia relieved by wearing a patch over one eye • Glaucoma suspect OU • Ophthalmic Medications: none • FOHx: unremarkable

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• PMHx: • Systemic Medications • Entrance Testing • PTSD • Fluoxetine HCL 20mg QD • VAcc • OD 20/25-1 • Hypertension • Lisinopril 40mg QD • OS 20/30+1 • Dyslipidemia • Simvastatin 40mg QD • Pupils: ERRL, (-) APD OU • Obesity • Terazosin HCL 1mg QD • EOMs: OD unable to adduct past midline with limited supraversion and • Pain in joint • Aspirin 81mg QD infraversion, FROM OS, diplopic except in right gaze • CVF: FTFC OU • Coronary artery disease • CT at distance: difficulty fixating with OD • Tobacco remission

• SLE • BP: • L/L: complete ptosis OD, dermatochalasis OS • 144/72 LAS @1218 in office • Conj: OU • Cornea: mild arcus OU • About 180/80 at ER after onset of diplopia • Angles: 2x2 OU • A/C: D&Q OU • Iris: patent PI @ 10:00 OD, 4:00 OS • Lens: 2+ NS OU • IOP: 22/20 @1148 GAT • DFE • Vit: syneresis OU • ONH: 0.5 OU, pink rims with distinct margins • Vessels: normal course and caliber OU • Macula: flat and dry OU • Periph: intact/no holes, tears, or detachments OU

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• Diagnosis: Pupil-Sparing Complete Right Third Nerve Palsy • Lab Results • Cause is likely ischemic • ESR/Westergren: 22mm/1hr • Negative CT in emergency department after onset • CRP: 4.53 mg/L • No GCA symptoms • A1c: 6.3 • History of EOM palsy OS 15-18 years prior

• Plan: ordered ESR, CRP and A1c; follow-up in 1 month • Of note, no clinics or hospitals in the area could perform a head MRI due to the patients implanted bladder stimulator

• Impression/Plan • CC: Right eye is no longer closed and headaches have • Isolated right CN 3 palsy: likely ischemic improved. Patient notes that he can move his eye more but still • known CAD has to wear the patch to prevent double vision. • recent unremarkable coronary angiogram • No change to POHx, FOHx, or PMHx • per recent CTA head/neck, no carotid stenosis and no intracranial • Medications aneurysm • Discontinued lisinopril • other possibility is a rare side effect of statin medications • Started amlodipine besylate 5mg QD • Started valsartan 40mg QD (to replace lisinopril)

• Entrance Testing: unchanged

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• SLE: • L/L: ptosis OD resolved, dermatochalasis OU • Conj: pinguecula OU • Cornea: mild arcus OU • Angles: 2x2 OU • A/C: D&Q OU • Iris: patent PI @ 10:00 OD, 4:00 OS • Lens: 2+ NS OU

• IOP: 20/21 @1518 GAT

• Assessment: Pupil-Sparing Complete Right Third Nerve Palsy, • CC: woke up about 1 week prior and vision seemed back to improved normal, no longer wearing the patch or seeing double • involvement resolved • Entrance Skills • Plan: monitor, follow-up in 1 month • VAsc • OD 20/80+2 PH 20/25-2 • OS 20/40+1 PH 20/25+2 • Pupils: ERRL, (-)APD OU • EOMs: FROM OU, no diplopia • CVF: FTFC OU • CT at distance: 18XP (without correction)

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• Assessment: Pupil-Sparing Complete Right Third Nerve Palsy, resolved

• Plan: Monitor; resume glaucoma testing

• lies in the midbrain at the level of the superior colliculus, ventral to the cerebral aqueduct • levator subnucleus: unpaired midline structure which innervates both levator muscles • superior rectus subnuclei: paired structures that innervate the contralateral superior rectus • medial rectus, inferior rectus, and inferior oblique subnuclei: paired structures that innervate the ipsilateral muscles

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• uncommon • passes through the red nucleus and the medial aspect of the • often associated with trochlear nerve nuclei cerebral peduncle, emerging into the interpeduncular space • most frequent: • vascular disease • primary tumors • metastases • involvement of the medial rectus subnuclei will cause a wall- eyed bilateral internuclear ophthalmoplegia

• Benedikt syndrome: involves the fasciculus as it passes through the red • passes between the posterior cerebral and superior cerebellar nucleus arteries, running parallel to the posterior communicating artery • characterized by ipsilateral 3rd nerve palsy with contralateral extrapyramidal signs such as hemitremor, hemiballismus and loss of sensation • Weber syndrome: involves the fasciculus as it passes through the cerebral peduncle • characterized by ipsilateral 3rd nerve palsy with contralateral hemiparesis • Nothnagel syndrome: involves the fasciculus and the superior cerebellar peduncle • characterized by ipsilateral 3rd nerve palsy with cerebellar ataxia and dysmetria • Claude syndrome: combination of Benedikt and Nothnagel syndromes

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• aneurysm: most commonly of the posterior communicating artery at its junction with the internal carotid artery • presents as an acute 3rd nerve palsy with pupil involvement • extradural or subdural hematoma: causes downward herniation of the temporal lobe, which causes causes compression of the nerve • ‘surgical’ lesions like aneurysms and trauma compress the pial blood vessels which causes pupillary involvement • ‘medical’ lesions like hypertension and diabetes spare the pupil because they affect the vasa nervorum which causes ischemia of the nerve trunk

• runs along the lateral wall of the cavernous sinus, above the • pituitary apoplexy trochlear nerve • intracavernous pathology: aneurysm, meningioma, carotid- cavernous fistula, granulomatous inflammation (Tolosa-Hunt syndrome)

• usually also involve the 4th and 6th cranial nerves and first division of the 5th nerve

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• enters the orbit through the annulus of Zinn in two branches • commonly traumatic or vascular for both the superior and • superior division: innervates the levator and superior rectus muscles inferior divisions • inferior division: innervates the medial rectus, inferior rectus and inferior oblique muscles • innervates the pupillary sphincter and ciliary muscle with preganglionic parasympathetic fibers from the Edinger-Westphal subnucleus

MUSCLE DIVISION PRIMARY ACTION SECONDARY ACTION • binocular diplopia inferior rectus inferior depression adduction, extorsion • eye turn inferior oblique inferior extorsion elevation, abduction • may have: pain, headache, droopy lid medial rectus inferior adduction superior rectus superior elevation adduction, intorsion levator superior eyelid elevation pupillary sphincter inferior ciliary muscle inferior accommodation

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• congenital: birth trauma or neurologic syndrome • regenerating neurons misdirected and reinnervate the incorrect • children: infection, postviral illness, trauma or tumor (commonly muscle pontine glioma) • may follow traumatic and compressive palsies • adults: • need a breach in nerve sheaths • idiopathic: 10-30% have no identifiable cause • vascular disease (e.g., hypertension, diabetes): 20-45% • does not occur in vascular palsies • spontaneous recovery usually occurs within 3 months • examples: • if due to diabetes, sometimes associated with periorbital pain • elevation of the upper eyelid on attempted adduction or depression • aneurysm of posterior communicating artery (15-20%) (pseudo-Graefe phenomenon) • could also be the superior cerebellar or posterior cerebral arteries • miosis with elevation or adduction (pupil-gaze dyskinesis) • other: tumors, syphilis, giant cell arteritis, collagen vascular disorders • brief episodes with spontaneous recovery • migraine, compression, ischemia, alterations in intracranial pressure • DDx: myasthenia gravis, thyroid ophthalmopathy, migraine, CPEO

• neurologic examination to see if other nerves are involved • treat underlying condition • check blood pressure • aneurysms, tumors and trauma may require neurosurgery • MRI and/or MRA if: • occlusion to alleviate diplopia • pupil involvement • Fresnel prism to neutralize the angle of deviation • associated with other neurologic abnormalities • botulinum toxin injection into the to prevent • pupil-sparing in young patients (<45 years old) contracture • signs of aberrant regeneration • surgical treatment after all spontaneous improvement has • no improvement in suspected microvascular cases after 3 months ceased, no earlier than 6 months from onset • lab tests: fasting blood glucose, CBC, ESR, VDRL, FTA-ABS, ANA • cerebral angiography in pupil-involved cases where MRI/MRA is inconclusive • lumbar puncture if subarachnoid hemorrhage is suspected

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• follow pupil-sparing lesions daily for the first week

• only cranial nerve to emerge from the dorsal aspect of the • located in the midbrain at the level of the inferior colliculus brain • lies anterior to the cerebral aqueduct and inferior to the • only cranial nerve to cross: nucleus innervates the contralateral oculomotor nucleus • long, slender nerve

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• travel dorsally and decussate • leaves the brainstem just inferior to the inferior colliculus • curves laterally around the brainstem and runs anteriorly beneath the free edge of the tentorium • passes between the posterior cerebral and superior cerebellar arteries

• runs in the lateral wall of the cavernous sinus • enters the orbit through the , superior and • lies between the oculomotor nerve and ophthalmic division of lateral to the annulus of Zinn the trigeminal nerve • innervates the superior oblique muscle

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• binocular vertical or diagonal diplopia, may have a torsional component MUSCLE PRIMARY ACTION SECONDARY ACTION superior oblique extorsion elevation, abduction • blurred vision • head tilt (toward contralateral side)

• congenital: common • Step 1: • symptoms may not develop until decompensation occurs in adulthood • asses which eye is hyperdeviated in primary gaze • family album tomography • could be caused by weakness of one the depressors of the hyper eye or • trauma: common (30-40%) one of the elevators hypo eye • bilateral lesions are often thought to be unilateral until surgery is performed, following which the contralateral nerve palsy is often revealed • in a 4th nerve palsy, the involved eye is hyper • vascular: common (20%) • aneurysms and tumors are extremely rare RSR RIO LIO LSR • idiopathic (30%) • DDx: myasthenia gravis, thyroid ophthalmopathy, orbital disease, CNIII palsy, Brown’s syndrome, skew deviation, superior oblique myokymia

RIR RSO LSO LIR

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• Step 2: • Step 3: Bielschowsky Head Tilt Test • determine whether the hyperdeviation is greater in right or left gaze • determine whether the hyperdeviation is greater with right or left head tilt

• in a 4th nerve palsy, the deviation is worse on opposite gaze • in a 4th nerve palsy, the deviation is better on opposite tilt

RSR RIO LIO LSR RSR RIO LIO LSR

RIR RSO LSO LIR RIR RSO LSO LIR

• different colored Maddox rods, with the cylinders vertical, are • neurologic examination to see if other nerves are involved placed one in front of either eye • check blood pressure • in the presence of cyclodeviation, the line perceived by the • MRI and/or MRA if: paretic eye will be tilted • history of head trauma • one Maddox rod is rotated until superimposition occurs • history of cancer • signs of meningitis • <10° of cyclodeviation indicates a unilateral palsy • young age • other neurologic abnormalities • >10° of cyclodeviation indicates bilateral palsy • no improvement in suspected microvascular cases after 3-4 months • lab tests: fasting blood glucose, CBC, ESR, VDRL, FTA-ABS, ANA • this can also be done in a synoptophore

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• treat underlying condition • 65 YOWM presents with sudden onset constant horizontal • muscle surgery if longstanding, stable diplopia in all gazes except right gaze, worse in left gaze, since • occlusion to alleviate diplopia waking on 12/21/14 • Left eye is turned inward • prism to neutralize the angle of deviation • Mild ache in back of the neck that morning but no longer remarkable • aneurysms, tumors and trauma may require neurosurgery • No other neurological symptoms • Patient reports systolic BP around 140 since diplopia started • Diplopia relieved by closing either eye or wearing a patch

• POHx • Systemic Medications • PMHx: • Chlorthalidone 25mg QD • History of mild NPDR OU • GERD • Erythromycin 2% solution • History of CME OS resolved after one intravitreal injection of Avastin • Insulin glargine 100 unit/mL • Colonic polyps • Lisinopril 40mg QD • Ocular Hypertension OU • Potassium chloride 10meq QD • Elevated PSA • Ophthalmic Medications: • Triamcinolone acetonide 0.5% cream • Hypertension • Aspirin 182mg QD • dorzolamide/timolol BID OU • Fish oil 2gm QD • bimatoprost QHS OU • Sleep apnea • Multivitamin

• FOHx: unremarkable • Anemia • Diabetes information • Diabetes mellitus type II • Diagnosed around 2001 (14 years) • Blood sugar 107 that morning, usually • Hypertriglyceridemia not higher than 130, A1c 3 months prior was 8.6 • Morbid obesity

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• Entrance Testing • VAsc: • OD 20/20-1 • OS 20/25 • Pupils: ERRL, (-)APD OU • EOMs: FROM OD, unable to abduct to midline OS, diplopia in left gazes • VF (gross): FTFC

• SLE: • DFE: • Diagnosis: Left Cranial Nerve VI Palsy • L/L: mild dermatochalasis OU • Vit: syneresis OD, PVD OS • likely ischemic as patient is being treated for diabetes and hypertension • Conj: clear OU • ONH: • no headache, nausea, vomiting, or GCA symptoms • Cornea: tr pigment on endo OU • OD: 0.45, no NVD, pink rim with distinct margins • no other neurologic symptoms • Angles: 4x4 OU • OS: 0.45, no NVD, pink rim with distinct • unable to measure BP as appropriately sized cuff was not available • A/C: deep and quiet OU margins • Iris: no holes/tears or NVI OU • Vessels: normal course and caliber, no VB • Lens: OD: tr NS, 1+CS OU • Plan: Order updated A1c, wear patch over OS; follow up in 6 OS: tr NS, 2+CS • P Pole: no heme/MA/CWS/IRMA/NVE OU weeks • Macula: few hard perimacular drusen OU, • IOP: 23/23@1337 GAT no CSME OU • Periph: intact/no holes, tears, or detachments 360 OU

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• CC: Double vision in left gaze only, no longer wearing the patch. Improvement started 02/20/14 • No change to POHx, FOHx, PMHx, or medications

• Entrance Testing: • VAcc: • OD 20/20-1 • OS 20/20 • Pupils: ERRL, (-)APD OU • EOMs: FROM OU, diplopia in left gaze • VF (gross): FTFC • Cover Test: distance: ortho

• Diagnosis: Left Cranial Nerve VI Palsy, improved

• Plan: monitor; RTC 3-4 months for HVF and IOP check to resume monitoring of ocular hypertension

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• located near the midline of the pons, ventral to the floor of the • contains internuclear neurons that communicate the contralateral 4th ventricle abducens nucleus via the medial longitudinal fasciculus • fasciculus of the 7th nerve curves around the abducens nucleus • connected to the contralateral medial rectus via the paramedial • isolated abducens palsy is never nuclear in origin pontine reticular formation, which coordinates conjugate horizontal eye movements

• ipsilateral weakness of abduction • leaves the brainstem at the pontomedullary junction • failure of horizontal gaze towards the side of the lesion (resulting from involvement of the horizontal gaze center in the PPRF) • ipsilateral lower motor neuron facial nerve palsy

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• Foville syndrome: involves the fasciculus as it passes through the • runs along the occipital bone at the base of the skull PPRF • travels over the petrous ridge of the temporal bone • most frequently caused by vascular disease or tumors • ipsilateral involvement of the 5th-8th nerves and central sympathetic fibers • 5th nerve – cranial anesthesia • 6th nerve palsy combined with gaze palsy • 7th nerve – facial weakness • 8th nerve – deafness • central Horner syndrome • Millard-Gubler syndrome: involves the fasciculus as it passes through the pyramidal tract • most frequently caused by vascular disease, tumors or demyelination • ipsilateral 6th nerve palsy • contralateral hemiplegia

• acoustic neuroma: may damage the abducens nerve at the • travels near the internal carotid artery pontomedullary junction • first symptom: hearing loss • first sign: decreased corneal sensitivity • nasopharyngeal tumor: may invade the skull at its foramina • raised intracranial pressure: stretches the abducens nerve at the petrous ridge • basal skull fracture • Gradenigo syndrome: damages the abducens nerve at the petrous ridge secondary to mastoiditis or petrositis • accompanied by facial weakness and pain and hearing difficulties • lesions are similar to those affecting the third nerve

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• enters the orbit through the superior orbital fissure within the MUSCLE FUNCTION annulus of Zinn lateral rectus abduction • innervates the lateral rectus muscle

• horizontal binocular diplopia • children: most commonly tumors or postviral • worse at distance than near • adults (>40 years old): trauma or microvascular disease • worse in the direction of gaze of the paretic muscle • most common isolated cranial nerve palsy in diabetes • also associated with multiple sclerosis, cerebrovascular accidents, increased intracranial pressure and rarely tumors

• DDx: myasthenia gravis, thyroid ophthalmopathy, Duane’s syndrome, orbital fracture with medial rectus entrapment, orbital myositis, convergence spasm, early-onset esotropia

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• neurologic examination to see if other nerves are involved • treat underlying condition • check blood pressure • aneurysms, tumors and trauma may require neurosurgery • MRI and/or MRA if: • occlusion to alleviate diplopia • patient is a child • Fresnel prism to neutralize the angle of deviation • history of head trauma or cancer • surgical treatment in longstanding, stable cases • signs of meningitis • association with other neurologic abnormalities • no improvement in suspected microvascular cases after 3-6 months • lab tests: fasting blood glucose, CBC, ESR, VDRL, FTA-ABS, ANA • lumbar puncture if elevated intracranial pressure is suspected

• depends on etiology • Kanski, Jack J. ”Neuro-Ophthalmology." Clinical Ophthalmology: • microvascular palsies tend to resolve within 3 months A Systemic Approach. Oxford: Butterworth Heinemann Elsevier, 1994. • Remington, Lee Ann. "Cranial Nerve Innervation of Ocular Structures." Clinical Anatomy and Physiology of the Visual System. 3rd ed. St. Louis, MO: Elsevier/Butterworth Heinemann, 2012. 218-32. • Wilson-Pauwels, Linda, P. A. Stewart, E. J. Akesson, and S. D. Spacey. Cranial Nerves: Function and Dysfunction. 3rd ed. Shelton, CT: People's Medical Pub. House, 2010. Web. 28 Mar. 2015.

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Keegan K Bench O.D. Keegan K Bench B.Sc. Resident Optometrist Recreational Herpetologist Mann-Grandstaff VAMC Amateur Photographer Spokane WA Spokane WA

Crotalus Molossus (Black-tailed Rattlesnake)

Right Hemianopsia Left Heminanopsia

en.wikipedia.org www.santarosa.edu

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 Ganglion Cell Complex/Analysis  Advancement with SD-OCT  Differences with various devices • Zeiss Cirrus • Optovue RTVue • Heidelberg Spectralis

brain.oxfordjournals.org [1]

GANGLION CELL LAYER + Uses normative data for comparison Does not include NFL

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GCC = NFL + GCL +IPL Uses normative data

www.oct-optovue.com/GCC-RTVue-version4.pdf www.oct-optovue.com/GCC-RTVue-version4.pdf

All retinal layers Larger area scanned (24-2 HVF) Compares differences between the eyes RNFL ANALYSIS GCA ANALYSIS

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10/24/13

44 yr old Hispanic male with POAG OD

10/24/13 10/24/13

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3/11/13

75 yr old White female with pituitary tumor, removed 6/13.

4/11/14

78 yr old White male with history of pituitary tumor.

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1/30/2013 1/15/13

1/15/13 1/15/13

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3/8/11

3/08/11 77 yr old White female Presents with blind spot OD beginning 6 months ago

3/6/12 4/14/14

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4/1/14 4/1/14

12/06/96

71 yr old White male with previously noted glaucoma defect. Stroke was found some time later.

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6/28/05 3/31/14

8/25/2010 8/25/2010

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 Chiasmal and lesions have been shown to present with RNFL loss.

 Congenital and longstanding occipital lesions can present with band atrophy and RNFL thinning.

 Cases of GCC loss that correlates to visual field loss due to cerebral infarctions.

[2]

[2] [2]

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[3] [3]

[3] [4]

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[4] [4]

 66 yr old male

 Hemorrhagic stroke May of 2013

 Unable to perform standard visual field testing

 Wolf Wand and CVF indicate left hemianopsia

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Visual Field 1 month after unspecified stroke showing right hemianopsia OD OS

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Michael Kalloniatis Michael Kalloniatis Director, Centre for Eye Health Director, Centre for Eye Health Professor, Optometry & Vision Science, UNSW Professor, Optometry & Vision Science, UNSW

[5] [5]

Michael Kalloniatis Director, Centre for Eye Health Professor, Optometry & Vision Science, UNSW

 Window of time before GCC detects changes due to various lesions  Tran-synaptic retrograde degeneration  GCC vs Retinal Thickness vs VF  Field resolution with and without GCC loss, ie brain and nerve plasticity  Other degenerative brain disease and GCC, ie MS and Alzheimer's

[5]

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 [1] Jindahra P, Petrie A, Plant GT. Retrograde trans-synaptic loss identified by optical coherence tomography. Brain. 2009;132:628-634.

 [2] Metha JS, Plant GT. Optical coherence tomography findings in Special thanks to… congenital/longstanding homonymous hemianopia. Am J Ophthalmol.  Vladimir Yevseyenkov O.D., Ph.D, FAAO 2005;140:727–9.  David A Kaplan O.D.  John A Nguyen O.D.  [3] Park HL, Park YG. Transneural retrograde degeneration of retinal ganlion cells in patients with cerebral infarction. Ophthalmalogy 2013;  Jessica Neuville O.D. FAAO 120:1292-9.

 [4] Yamashita T, Asushi M. Reduced retinal ganglion cell complex And the entire Spokane VA Eye Clinic Staff thickness in patients with posterior cerebral artery infarction detected using spectral-domain optical coherence tomography. Jpn J Ophthalomol. 2012; 56:502-10.  [5] Zangerl el al OVS submitted and Kalloniatis personal communication. Contact information… [email protected]

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