Kansas EyeCon

2016

Kan

sas

EyeC

on

Sponsored by the University of Kansas Department of Ophthalmology

and the Lemoine Alumni Society

April 8 & 9, 2016 The Venue

4800 W 135th St., Ste. 108 Leawood, KS 66209

DEPARTMENT OF OPHTHALMOLOGY SCHOOL OF MEDICINE CLINICAL FACULTY

kumed.com/kueye

C. Scott Atkinson, MD Miranda Bishara, MD Dirck DeKeyser, OD William Godfrey, MD Pediatric Ophthalmology Cornea/Refractive/Cataracts Optometrist Uveitis

Shree Kurup, MD Paul Munden, MD Ajay Singh, MD Jason Sokol, MD Retina and Vitreous Glaucoma & Anterior Segment Retina and Vitreous Oculofacial Plastic & Orbital Surg.

John Sutphin, MD, Chair Matthew Twardowski, O.D. W. Abraham White, MD Thomas J. Whittaker, JD, MD Cornea & Anterior Segment Optometrist Comprehensive Neuro-Ophthalmology

7400 State Line Rd Prairie Village, KS 66208 Appointments: 913-588-6600

3901 Rainbow Blvd., Ste. 1011 Miller Kansas City, KS 66160

Appointments: 913-588-6688

DEPARTMENT OF OPHTHALMOLOGY SCHOOL OF MEDICINE RESIDENTS

2015 – 2016

Third-Year Residents

Anna Berry, MD Michelle Boyce, MD Lillian Yang, MD Pager: 0369 Pager: 0418 Pager: 1488

Second-Year Residents

Derek Horkey, MD Anjulie Quick, MD Robert Null, MD Pager: 4935 Pager: 0404 Pager: 0732

First-Year Residents

Luke Dolezal, MD Joshua Jones, MD Reid Mollman, MD Pager: 2016 Pager: 1487 Pager: 0447

EDUCATING TOMORROW’S GENERATION ~ CARING FOR TODAY’S

KansasEyeCon2016Wewishtoacknowledgeandsincerelythank

theseorganizationsforexhibitingatthisconference:

PlatinumSponsors:

AlconLaboratories,Inc.Ellex

EnhancedMedicalServicesHeidelbergEngineering

RegeneronPharmaceuticals,Inc.ShireMedicalAffairs

SilverSponsors:

Allergan,Inc.Bio‐Tissue

CarlZeissMeditec,Inc.

BronzeSponsor:

KUAudio‐ReaderNetwork

Kansas EyeCon 2016 The Venue

4800 W 135th St., Ste. 108 Overland Park, KS April 8 & 9, 2016

Program Overview ‐ This conference is intended to provide ophthalmologists with an educational forum to learn about new developments in the profession and their application to patient care. Covering a cross‐section of all sub‐specialties, physicians can expect to walk away having heard evidence‐based presentations.

Target Audience ‐ This program is designed to meet the needs of practicing ophthalmologists.

Learning Objectives ‐ Upon completion of the educational activity, participants should be able to: Orbital Session

1. Provide an overview of the indications, history, symptoms, biopsy results and outcomes of patients with suspected giant cellarteritis;

2. Evaluate the efficacy and utility of temporal artery biopsies performed at the University of Kansas Hospital;3. Describe the clinical presentation of orbital myeloid sarcoma;4. Describe the natural history of the disease, as well as the available treatments; 5. Recognize the most common periorbital skin malignancy associated with immunosuppressive therapy;6. Determine if periorbital skin malignancies while on immunosuppressive therapy result in a higher incidence of exenteration;7. Outline the most common reasons for eye destructive procedures in a tertiary care center;8. Recognize the most common neoplasms requiring eye destructive procedures; 9. List two major potential benefits of virtual reality technology in vision science;10. Explain the outcomes of some virtual reality‐based interventions to improve visual scanning capabilities of patients with low

vision.Cataract and Pediatric Session

11. Understand the role of microtropia in the spectrum of diplopia, strabismus and peripheral fusion;12. Diagnose microtropia using the Bruckner red reflex test, Bagolini lens test, base out prism test and stereo testing; 13. Recognize Cataract surgery difficulties and solve these problems, or at least better manage them when they occur;14. Identify several ways the ophthalmologist will learn over time to improve the quality of eye care for the patients served by

embracing personal education through reading, personal observation and experience;15. Learn new insights to enhance surgical outcome with cataract surgery.

Anterior Segment and Refractive Session 16. List two advantages to the use of femtosecond laser for use in posterior polar cataract extraction;17. Implement essential surgical steps to reduce complications in removal of posterior polar cataract;18. Describe the three stages of the Dysfunctional Lens Syndrome; 19. List the advantages of Refractive Lens Exchange surgery;20. Understand the timing and approaches to surgery in complex uveitis;21. Diagnose uveitis patients who benefit with vitreoretinal surgery;22. Describe risk factors for intraocular pressure elevation after dexamethasone intravitreal injection;23. Discuss treatment interventions for increased intraocular pressure after dexamethasone intravitreal injection;24. Provide a differential diagnosis for posterior uveitis;25. Describe the pros and cons of treatment options for chronic posterior uveitis;26. Describe what functional visual changes occur in diabetic retinopathy prior to development of visible vascular lesions;27. State which cell types in the retina are involved in early diabetic retinopathy;28. Discuss the effects of diabetes on the ocular surface and patient reported dry eye symptoms; 29. Discuss the correlation in diabetic patients of ocular surface disease, severity of diabetic retinopathy and a history of retinal laser

treatment;30. Analyze results of clinical trials in diabetic macular edema and apply them to clinical practice;31. Manage patients with anti‐VEGF and steroid‐based therapies through the preferred dosing practices;32. Recognize the protective effect of fenofibrate on progression of diabetic retinopathy;33. Describe what driving forces generate the excess of vascular endothelial growth factor in advanced stages of diabetic retinopathy;34. Summarize the interpretation of visual fields obtained by static perimetry and describe how static automated perimetry can be

used over time to monitor for glaucomatous changes in a clinical setting;35. Describe the artifacts introduced with simulated afferent pupillary defects during automated perimetry field testing;36. Generate and interpret Humphrey Field Analyzer GPA reports;37. Use the event and trend analysis GPA functions to determine the likelihood of progressive visual field loss in glaucoma patients.

Method of Participation Statements of credit will be awarded based on the participant's attendance and submission of the activity evaluation form. A statement of credit will be available upon completion of an activity evaluation/claimed credit form that should be turned it at the end of the meeting. If you have questions about this CME activity, please contact AKH Inc. at [email protected].

CME Credit Provided by AKH Inc., Advancing Knowledge in Healthcare Physicians

This activity has been planned and implemented in accordance with the Essential Areas and policies of the Accreditation Council for Continuing Medical Education (ACCME) through the joint providership of AKH Inc., Advancing Knowledge in Healthcare and the University of Kansas, Department of Ophthalmology and The Lemoine Alumni Society. AKH Inc., Advancing Knowledge in Healthcare is accredited by the ACCME to provide continuing medical education for physicians.

AKH Inc., Advancing Knowledge in Healthcare designates this live activity for a maximum of 7.0 AMA PRA Category 1 Credit(s)™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

FACULTY DISCLOSURES

Name Relationship Commercial Interest

Abiodun E. Akinwuntan, PhD, MPH, MBA N/A Nothing to Disclose

Michelle Boyce, MD N/A Nothing to Disclose

Gerhard Cibis, MD N/A Nothing to Disclose

Luke Dolezal, MD N/A Nothing to Disclose

Luther Fry, MD N/A Nothing to Disclose

Derek Horkey, MD N/A Nothing to Disclose

John Hunkeler, MD N/A Nothing to Disclose

Joshua Jones, MD N/A Nothing to Disclose

Shree Kurup, MD N/A Nothing to Disclose

Reid Mollman, MD N/A Nothing to Disclose

Paul Munden, MD N/A Nothing to Disclose

Robert Null, MD N/A Nothing to Disclose

Anjulie Quick, MD N/A Nothing to Disclose

Rithwick Rajagopal, MD N/A Nothing to Disclose

Chetan Soni, MD N/A Nothing to Disclose

Jason Stahl, MD N/A Nothing to Disclose

Natalia Villate, MD N/A Nothing to Disclose

Lillian Yang, MD N/A Nothing to Disclose

PLANNER DISCLOSURES

KUMC/KSEPS Staff and Planners N/A Nothing to Disclose

AKH Staff and Planners N/A Nothing to Disclose

Commercial Support There is no commercial support for this activity.

Disclosures It is the policy of AKH Inc. to ensure independence, balance, objectivity, scientific rigor, and integrity in all of its continuing education activities. The author must disclose to the participants any significant relationships with commercial interests whose products or devices may be mentioned in the activity or with the commercial supporter of this continuing education activity. Identified conflicts of interest are resolved by AKH prior to accreditation of the activity and may include any of or combination of the following: attestation to non‐commercial content; notification of independent and certified CME/CE expectations; referral to National Author Initiative training; restriction of topic area or content; restriction to discussion of science only; amendment of content to eliminate discussion of device or technique; use of other author for discussion of recommendations; independent review against criteria ensuring evidence support recommendation; moderator review; and peer review.

Disclosure of Unlabeled Use and Investigational Product This educational activity may include discussion of uses of agents that are investigational and/or unapproved by the FDA. Please refer to the official prescribing information for each product for discussion of approved indications, contraindications, and warnings.

Disclaimer This course is designed solely to provide the healthcare professional with information to assist in his/her practice and professional development and is not to be considered a diagnostic tool to replace professional advice or treatment. The course serves as a general guide to the healthcare professional, and therefore, cannot be considered as giving legal, nursing, medical, or other professional advice in specific cases. AKH Inc. specifically disclaim responsibility for any adverse consequences resulting directly or indirectly from information in the course, for undetected error, or through participant's misunderstanding of the content.

LEMOINEDISTINGUISHEDALUMNILECTURERS

LECTURER TITLE DATE

TimothyW.Olsen,MD RockChalkRetinaTalk:100yearKU 5/9/2014KUSOMMD‘89

LutherL.Fry,MD StandardCataractSurgery:Tips&Tricks 5/8/2015KUSOMMD‘67 Learnedafter40,000+Cases

JohnD.Hunkeler,MD ContinuousEducation 4/8/2016KUSOMMD‘67KUEyeResidency‘73

AlumniSpeakers

LutherL.Fry,MDMD:1967

JohnD.Hunkeler,MDMD:1967;Residency:1973

NataliaVillate,MDResidency:2008

AGENDA

Kansas EyeCon April 8 - 9, 2016

The Venue 4800 W 135th St., Ste. 108

Leawood, KS 66209

Friday, April 8, 2016

12:00 p.m. Registration and lunch with exhibitors

1:00 p.m. Welcome: Miranda Bishara, MD

Orbital Session

1:05 p.m. Lillian Yang, MD, Temporal Artery Biopsy Outcomes in Patients with Suspected Giant Cell Arteritis

1:15 p.m. Reid Mollman, MD, Bilateral Orbital Myeloid Sarcoma in an Adult with Recurrent AML

1:25 p.m. Joshua Jones, MD, Recurrent Squamous Cell Carcinoma with Orbital Invasion (some requiring exenteration) in the Setting of Immunosuppression Following Organ Transplants – Case Series

1:35 pm Derek Horkey, MD, Retrospective Review of Indications of Evisceration, Enucleation or Exenteration at one Academic Institution

1:45 p.m. Abiodun Akinwuntan, MD, Virtual Reality Technology and Vision

Cataract and Pediatric Session

2:35 p.m. Gerhard Cibis, MD, Microtropia (Lang); Monofixation(Parks): Prevalence, Significance, Evolution, Diagnosis with the Bruckner Red Reflex Test

3:00 p.m. Break

3:30 p.m. Luther Fry, MD, Common Cataract Surgery Difficulties: How to Avoid or Manage Them

3:55 p.m. Introduction of Dr. Hunkeler: Luther L. Fry, MD

4:00 p.m. John Hunkeler, MD, Lemoine Distinguished Alumnus Lecturer, Continuous Education

5:00 p.m. Session Adjourns

Onsite reception immediately following

University of Kansas Department of Ophthalmologyand The Lemoine Alumni Society

Kansas EyeCon April 8 – 9, 2016

Saturday, April 9, 2016

7:30 a.m. Breakfast with exhibitors

7:30 a.m. Michael Ellis, MS4, A Rapid Cycle Quality Improvement Project: Implementation of Diabetic Retinopathy Screening in a Primary Care Setting Using Tele-Ophthalmology

8:00 a.m. Welcome – Miranda Bishara, MD

Anterior Segment and Refractive Session

8:05 a.m. Chetan Soni, MD, Femtosecond Laser Assisted Cataract Extraction of Posterior Polar Cataracts

8:25 a.m. Jason Stahl MD, Refractive Lens Exchange

8:50 a.m. Shree Kurup, MD, Macular Surgery in Posterior Uveitis

9:15 a.m. Anjulie Quick, MD, Risk Factors for Intraocular Pressure Elevation After the Dexamethasone Intravitreal Injection

9:25 am Luke Dolezal, MD, Pattern Dystrophy: Case Series

9:35 a.m. Rithwick Rajagopal, MD, A Neurologic Perspective on Diabetic Retinopathy

10:00 a.m. Break

10: 25 a.m. Michelle Boyce, MD, Tear Osmolarity in Diabetic Patients

10:35 a.m. Natalia Villate, MD, Update on Diabetic Retinopathy and DME Management

11:00 a.m. Rithwick Rajagopal, MD, The Microvascular Pathology of Diabetic Retinopathy

11:25 am. Robert Null, MD, Effects of Simulated Afferent Pupillary Defect on Automated Perimetry

11:35 a.m. Paul Munden, MD, Detecting Functional Change in Progressing Glaucoma; Visual Field Guided Progression Analysis (GPA)

12:00 p.m. John Sutphin, MD, Luther and Ardis Fry Professor and Chairman, Closing Remarks: Future of KU Eye

12:15 p.m. Session Adjourns

University of Kansas Department of Ophthalmology and The Lemoine Alumni Society

ABSTRACTS

TemporalArteryBiopsyOutcomesinPatientswithSuspectedGiantCellArteritis

LillianYang,MD,Resident,Classof2016PrimarySupervisor:JasonSokol,MD

Giantcellarteritis(GCA)isasystemicdiseasethatcanhavedevastatingophthalmicconsequences.

Thediagnosisisbasedonclinicalcharacteristicsandestablishedbythepresenceofinflammatory

markers.However,theonlyspecificdiagnostictestisatemporalarterybiopsy(TAB).Although

uncommon,complicationsrelatedtoTAB,suchaspostoperativehematoma,scalpnecrosis,wound

infection,damagetofacialnerve,anddroopingofeyebrow,canoccur.Additionally,TABasa

diagnostictoolforGCAisnotperfectlysensitive,withreportedratesof70–90%.Thispresentation

isintendedtoreviewresultsfromtemporalarterybiopsiesperformedattheUniversityofKansas

HospitalandtodeterminetheirutilityindiagnosingGCA.

BilateralOrbitalMyeloidSarcomainanAdultPatientwithRecurrentAcuteMyeloidLeukemia(AML)

ReidMollman,MD,ResidentClassof2018PrimarySupervisor:JasonSokol,MD

Objective:

Here,wediscussasinglecaseofMyeloidSarcoma,alsopreviouslyreferredtoaschloromaorgranulocyticsarcoma,whichmanifestedasbilateralorbitalmassesinanadultwithrecurrentAML.

Method:

PresentationofasinglecaseofbilateralorbitalMyeloidSarcomainanadultwithrecurrentAML.

Results:

ThepatientinthiscasepresentedwithsubstantialproptosisandophthalmoplegiasecondarytolargebilateralMyeloidSarcomaorbitalmassesinthesettingofrecurrentAML.Sixweeksaftertreatmentwithintrathecalchemotherapy,aswellasradiation,thepatienthadvirtuallycompleteresolutionoftheorbitalmasses.

Conclusion:

Thisisaninterestingandrarecase,whereanadultpatientpresentedwithbilateralorbitalMyeloidSarcoma.Itisveryrareformyeloidsarcomatopresentintheorbit,and,makingthiscaseevenrarer,isthepresentationinanadult.Uponliteraturereview,itappearsthatonlyapproximately20casesofthisnaturehavebeendescribedinthepasttwodecades.

RecurrentSquamousCellCarcinomawithOrbitalInvasion(somerequiringexenteration)intheSettingofImmunosuppressionFollowingOrganTransplants–CaseSeries

JoshuaJones,MD,ResidentClassof2018PrimarySupervisor:JasonSokol,MD

Purpose:Reviewcurrentliteratureonanti‐graftmedicationpharmacologyanddiscusstheincreasedriskofsquamouscellcarcinomaintransplantpatients,alongwithretrospectivelyreviewingcasesinwhichtransplantpatientsweretreatedbyaninterdisciplinaryteam,includingOculoplasticsandOtolaryngologyforsquamouscellcarcinomawithorbitalinvolvement.

Design:Chartswereanalyzedfromfourpatientswhounderwentsurgicalresection,someradical,fortreatmentofsquamouscellcarcinomafollowingimmunosuppressivetherapyfortransplantsbetween2011and2016,recordingtheassociationwiththetypeofimmunosuppressivemedicationandbloodlevels,extentofinvasionofthetumorsandtypeofprocedurerequiredforeffectivetreatment.

Setting:OphthalmologyDepartmentatauniversity‐hospitalsetting

Patients:Amongthe4patientsincluded,averageagewas62yearsold;2weremaleand2werefemale.Onepatientwasdeceasedatthetimeofretrospectivereview,duetometastaticdisease.Eachpatienthadadifferenttypeoftransplant,suchasheart,liver,kidneyorbonemarrow.Theaveragetimeatinitialdiagnosisofsquamouscellcarcinomawas6.3yearsfollowinginitiationofanti‐graftmedication.

Conclusions:Squamouscellcarcinomaisasignificantcauseofmorbidityandmortalityforpatientsonlongtermimmunosuppressionfollowingotherwisesuccessfultransplants.Inourseriesof4patients,50%requiredlifesavingradicalsurgicalresection,includingexenteration.Evenwithasuccessfulsurgery,therateofmortalityishigh,giventheextentofinvasion.Ourfindingsconfirmwhatotherstudieshaveshown:thatthesepatientsneedtobemonitoredcloselyforsignsofperi‐orbitalmalignancyandtreatmentshouldnotbedelayed,giventhehighratesofrecurrenceandtissueinvasion.

RetrospectiveReviewofIndicationsofEvisceration,EnucleationorExenterationatoneAcademicInstitutionDerekHorkey,MD,ResidentClassof2017PrimarySupervisor:JasonSokol,MDPurpose:Attimesinophthalmology,insteadofvision‐enhancingorvision‐preservingprocedures,itisnecessarytoperformeyedestructiveprocedures,includingevisceration,enucleation,andexenteration.Thepurposeofthisstudywastoanalyze,overafiveyearperiod,thenumberofeyedestructiveproceduresandinvestigatethemostcommonindicationforsaidprocedures.Methods:AfterobtainingIRBapproval,allmedicalrecordsfromAugustof2010‐Februaryof2015frompatientshavingeyedestructiveproceduresperformedbyonesurgeonatoneacademictertiarycarefacilitywerereviewed,investigatingclinicalindicationfortheprocedure.Results:Therewere103eyedestructiveproceduresperformedon101patientsatoneinstitutionovertheroughly5yearperiod.Ofthese103,69%oftheprocedureswereenucleations,27%wereexenterationsand4%wereeviscerations.Thetwomostcommonindicationsforprocedureweretrauma(40%)andmalignancy(34%).Theothernotedindicationswereblindpainfuleye(15%),infection(10%)andrupturedcornea(1%).Discussion:Asonemightimagine,morecomplicatedcaseswereverycommonindicationsforeyedestructiveproceduresatatertiarycarecenter.ThehospitalisalevelItraumacenter,whichwouldaccountforahighvolumeoftraumacases.Also,giventhatthereisalargecancercenter,thehighincidenceofmalignancyisaccountedforaswell.Therewerealsofiveexenterationsperformedbecauseofinvasivemucormycosis.Inthesefivepatients,fourhadknownmalignanciesandonehadimmunodeficiency,secondarytounknownreason,whichwasbeingworkedupatthepatient’stimeofdeath.Thesenumberssuggestthatoftencomplicatedorbitaltraumaandmalignanciesaretransferredorreferredtotertiarycarecentersfordefinitivemanagementandtreatment.Ourinstitutionhasalargecancercenter,whichcontributestooursignificantnumberofproceduressecondarytothosemalignancy,aswellasmalignancyrelatedinfections.

References:

1. Hansen,AnjaBech,etal."Reviewof1028bulbareviscerationsandenucleations,Changesinaetiologyandfrequencyovera20‐yearperiod."ActaOphthalmologicaScandinavica77.3(1999):331‐335.

2. Rasmussen,MarieLouiseRoed,etal."Reviewof345eyeamputationscarriedoutintheperiod1996–2003,atRigshospitalet,Denmark."Actaophthalmologica88.2(2010):218‐221.

3. Zheng,Chengjie,andAlbertY.Wu."Enucleationversuseviscerationinoculartrauma:aretrospectivereviewandstudyofcurrentliterature."Orbit32.6(2013):356‐361.

4. Vemuganti,GeetaK.,etal."EnucleationinatertiaryeyecarecentreinIndia:prevalence,currentindicationsandclinico‐pathologicalcorrelation."Eye15.6(2001):760‐765.

Virtual Reality Technology and Vision

by

Abiodun E. Akinwuntan, PhD, MPH, MBADean and Professor

School of Health Professions

The University of Kansas Medical Center

NFB Blind Driver Challenge Video ‐ YouTube

Introduction

• Driving is an IADL that is very crucial in the US

• Vision is a critical component of driving

• It contribute > 90% of sensory input to driving

• Vision disorders at the or at the elevate risk to

driver safety

• Further complicated by aging (baby boomers) of the population

Vision

• Some visual conditions/diseases that impact driving ability

– Macular degeneration ‐ Stroke

– Retinitis pigmentosa ‐Multiple sclerosis

– Glaucoma ‐ Alzheimer’s disease

– Diabetic retinopathy ‐ Parkinson’s disease

– Cataracts ‐ Head trauma

– Post‐surgery ‐ Sleep disorders

Vision

• Common visual problems that impact driving ability

– Static and dynamic visual acuity ‐ Depth perception

– Visual field (central & peripheral) ‐ Color perception

– Speed of visual processing ‐ Contrast sensitivity

– Attention (divided, selective, sustained) ‐ Glare sensitivity

– Anopia ‐ Diplopia

Assessments for driving

• Typical ‐ Visual acuity and Perimetry (state driving laws)

• Driving‐related

– Perception (color & depth)

– Sensitivity (contrast & glare)

– Useful Field of View (UFOV)

– Cognitive (memory, search, spatial)

– Driving (simulator and on‐road)

• 7 Patients with age‐related macular degeneration

• Investigate the effect of training on driving

performance

• Rehabilitation consisted of 10 hours of static versus

dynamic vision training

First studyDynavision apparatus The Useful Field of View apparatus

plus

Driving Simulator

Overtaking

Hazard perception

Lane positioning

Road sign recognition

Brake reaction time

Anticipation

Akinwuntan et al, Arch Phys Med Rehabil, 2014

Result

cognitive workload

= degree of mental effort needed to execute a task

electroencephalogramPupillometry

Maud Ranchet, John Morgan, Abiodun E. Akinwuntan, Hannes Devos

Visual exploration and cognitive workload during a visual search task in individuals with PD

To investigate differences in visual search performances between patients with

Parkinson’s disease, with or without cognitive impairment and control volunteers

To explore cognitive workload during an efficient visual search

Objectives

FOVIO Eye tracker

10 controls 17 individuals with Parkinson’s disease

‐ 9 pa ents with a MOCA score ˃ 26 – Patients with no cognitive impairment (NCI)

‐ 8 patients with a MOCA score ≤ 26 – Patients with mild cognitive impairment (MCI)(Age controls: 65.1± 8.4 patients‐NCI: 65.0 ± 9.1, patients‐MCI: 71.3 ± 7.6, p>0.05)

Eye tracking 60 Hz

Fixation duration

cognitive workload measures changes in pupil dilation = reliable

estimate of mental effort (Marshall et al., 2000).

Values range from 0 to 1

Methods

Left eye

Right eye

ABSENT PRESENT

Visual search task

Pre‐identified target

42 trials 21 trials with target present15 s per trial

Outcomes:

Correct responses; Errors; Omissions; Correct response times

Fixation duration; Cognitive workload (0‐1)

Results

Res

pons

e tim

es (s

)

Controls Patients - NCI Patients- MCI

Mean SD Mean SD Mean SD p-value (2-tailed)Number of correct responses 36.5 3.5 36.6 4.1 31 5.8 0.049Number of errors 4.6 3.2 3.4 4.1 5.3 2.7 0.21Number of omissions 0.9 1.5 1.5 1.9 5.6 6.1 0.12Correct Response times 7.3 1.4 8.1 1.4 9.4 1.7 0.01

Cor

rect

resp

onse

s (m

ax s

core

= 4

4), n

010203040

Controls Patients -NCI

Patients -MCI

*

*

02468

1012

Controls Patients -NCI

Patients -MCI

**

No significant differences between the 3 groups for fixation duration and cognitive workload for the whole task (p > 0.05)

Results- Average cognitive workload of both eyes - Data normalized (0% -100%)

00.20.40.60.8

1

0% 20% 40% 60% 80% 100%

controls

% of response times

cogn

itive

wor

kloa

d

Moment of stimulus onset moment of response= press the “present” button

9 controls, 5 patients-NCI, 7 patients-MCI

DiscussionLarger sample sizes

The cognitive workload good marker of early cognitive decline in individuals with

Parkinson’s disease with no cognitive impairment apparent

CONTROLS PATIENTS WITH NO APPARENTCOGNITIVE IMPAIRMENT

Performance-Based Visual Field Testing in Drivers with Glaucoma

19

Methods

Driving simulator desktop

4 scenarios => Test the visual field performance with a visual field of 100 degrees

Main task: while focusing on the white square or the lead vehicle, hit the trigger button as soon as a red square appears

Eye tracker Control the eye movement of participants Measure the impact of cognitive workload on visual field outcomes

100°

FOVIO ‐ Eyetracker

20

First scenario: C1

Task:

Focus on the white square and press the button as soon as a red square appears

Aim: To investigate the effect of visual field performance

21 22

Second scenario: C2Aim: To investigate the effect of dynamic condition (visual flow)

Task: White central fixation point has been replaced by lead vehicleAutomatic pilot at 45 mphFocus on the lead vehicle and press the button for each red symbol

23 24

Third scenario: C3Aim: To investigate the effect of driving activity on the visual field performance

Task: The participant has follow a lead vehicle driving 45 mphSpeed warnings if the driver is above 50 or below 40 mphRandom wind gusts to keep driver attentivePress the button for each red target symbol

25 26

Fourth scenario: C4Aim: To investigate the effect of driving context on the visual field performance

Task: Drive while obeying all traffic rulesPress the button for each red target symbol

27 28

Expected results

‐ Poorer performances of visual field tests in

glaucoma patients compared to controls

‐ The C4 scenario will be a better predictor of

driving performances for glaucoma patients

‐ The cognitive workload will be associated to

visual field performances

29

Visual Field (VF) and Driving

‐ 36 states in the US have binocular horizontal VF requirements (15 = 1400; 18 = 1050‐1300; 1 = 1500)

‐ Kansas and Arkansas further specified the horizontal VF requirement for drivers with only one useful eye (550‐1050)

‐ 16 states: None except fails a visual acuity test or using special telescopic lenses and has been referred for further testing by an ophthalmologist or optometrist

‐ Only 1 state has vertical VF requirement

‐ In 2 states, no driver’s license for a person with homonymous hemianopia

30


31


32

‐ Healthy drivers

‐ 10 visual field deficits

‐ Interpupillary distance

and facial anatomy

Thank you and questions

Gerhard W. Cibis MD

Clinical Prof. Ophth. KU EyeEmeritus Chief CMH

Prevalence,SignificanceEvolution,Diagnosis with the

Brueckner red reflex test

Microtropia (Lang)Mono fixation (Parks)

• 40% of treated esotopes (surgery orglasses) end up microtropic

• Traditional tests for microtropia areimpossible in children

• Bruckner red reflex helps identifymicrotropes

Pupil Red Reflex"Brueckner Test" Indicates Fixation

StrabismusRefractive Error

•

• Superior Crescent fromHyperopia Aligned by

Hirschberg• Hyperopic Superior Crescent

Disappears with glasses correction

Inferior Myopic Crescent OUOD Hyperopic crescent +5

Cherry Red OS +1.5 minimal crescentOrthotropic 3/3 Lang Stereo

Not Accommodating Aligned

• OD ET Accommodating

OS Mic ET

OD Mic ET

Alternating Mic ET

• Not Accommodating no Crossing

• OD ET OS Fixing17year old modest myope acute onset diplopia

alternating esotropia• Still Microtropic with 18 BO Prism

L Mic ET

Residual R Mic with 18 BO prismno diplopia

Lenses sees two lights and streaks OS fix

18 BO Prisms over Bagolini lenses sees one light streaks form an X

gap in left streak confirms L suppression scotomaL mic.

• 17 year old female with myopia. Microtropia never recognized. Sudden onset ET with

diplopia

• Tumor workup and consternation as to what is going on

• Broken Down microtrope

• May need surgery

• Microtropia (Lang) aka Monofixation (Parks)

• Deviation of no more than 8-10 prism diopters

• Usually ET but XT mic. exists

• Central suppression scotoma in the deviated eyeallows for “peripheral fusion” without diplopia

• Suppression scotoma in the deviated eye allowsfor the following characteristics

• Fusion of Worth 4 dot lights at near where theyfall outside of the suppression scotoma but not at

distance where a light falls within the scotoma

• Steroacuity between 3000-60 seconds arc onTitmus but zero on Lang or other Random Dot

Stereograms

• 4 diopter base out prism displaces the imagewithin the suppression scotoma when held in front

of the microtropic eye therefore no fixation shift

• Held in front of the fixing eye both eyes shifts torefixate the target but the microtropic eye fails to

reconvert

• These observations are very hard in practiceimpossible on squirmy young children compared to

red reflex observations

• Cibis-Tongue A., Cibis GW: Brückner Test. Ophthalmology; 88:1041-1044,1981.

• Cibis GW, Tongue AC, Stass-Isern M: Decision Making in Pediatric Ophthalmology, C.V. Mosby Co.(St Louis), 1993.

• Cibis GW: Strabismus. Lang J., Slack Pub., translation from German into English, 1983.

• Cibis GW: Video vision development assessment (VVDA): Combining the Brückner test with eccentric photorefraction for dynamic identification of

amblyogenic factors in infants and children. Tr Am Ophth Soc; XCII:644-685, 1994 .

• Cibis GW: Video Vision Development Assessment In Diagnosis and Documentation of Microtropia. Binocular Vision Strabismus Quarterly; #20:

151-158.

• Cibis GW: Microtropia letter to the editor Binocular Vision & Strabismus Quarterly,#21 (2): 77, 2006.

• Cibis GW (2011). Chapter 5: Binocular Vision. In Lippincott, Williams and Wilkins (Eds.) Duane’s Ophthalmology 2011.

• The Decompensated Monofixation Syndrome:R. Michael Siatkowski MD Trans AmOphthalmic Soc 109:2232 -250, 2011

• Parks MM. The monofixation syndrome. Trans Am Ophthalmol Soc 1969;67:609-657.

• Lang J. Die Bedeutung des primären Mikrostrabismus für die Entstehung des Schielens. Klin Monatsbl Augenheilkd

• 1967;151:352-361.

• Lang J. Microtropia. Int Ophthalmol 1983;6:33-36.

CommonCataractSurgeryDifficulties:HowtoAvoidorManageThem(videopresentation)

LutherFry,MDVolunteerFaculty,KUEye

Effectofocularhypotensivedropsgivenimmediatelyaftercataractsurgeryon3‐and24‐hourpost‐opIOP.

Summaryofourmultiplestudies;8studies,approximately1000patients,scatteredoverthepast3years.

CosoptBEST,Combigan,SimbrinzaandTimolol0.5%next,TrusoptandAlphagannext.

Pilocarpine2%,Betoptic‐SandLumiganNOBETTERthancontrol(artificialtears).

SystemiccarbonicanhydraseinhibitorsNOBETTERthantopical.

Genericsasgoodasbrandname.

So,wenowuse:genericCosoptfornon‐asthmatics;SimbrinzaforasthmaticsandNOsystemicCAIs.

Notes:

Continuous Education

John D. Hunkeler, MD

April 8, 2016

Albert N. Lemoine Jr.

• Professor and Chairman

• Department of Ophthalmology

• University of Kansas School of Medicine

• 1950‐1980

Personal Interaction

• Medical School= Dr. Lemoine

• Residency= “Chief”

• Volunteer Faculty= “Al”

Al Lemoine

• Family Man

• Clinician

• Educator

• Leader

Clinician

• Premier cataract surgeon

• Excellent diagnostician

Educator

• Medical students and residents

• Massachusetts Eye and Ear InfirmaryLancaster Course

Leadership

• KU Chairman

• Recruited volunteer faculty, his practice included

Notable Faculty

• James T. Robison‐ retina

• Earl Padfield‐ glaucoma

• Sam Jones‐ peds and pathology

• L.L. “Fred” Hyde‐ cornea/cataract

Returning Fellows as Faculty

• Jerry Wurster

• Bill Godfrey

Personal Post Graduate Mentor

• Private practice with Fred Hyde

• Micro surgery pioneer

• Penetrating Keratoplasty triple procedure

• Planned extracapsular cataract extraction

International Mentors

• Charles Kelman

• Harold Ridley

• Daniele Aron‐ Rosa

• Dick Kratz

• Bob Sinskey

• Steve Shearing

• Tom Mazzocco

• Manus Kraff

Cataract Surgical Technique

• Intracapsular Cataract Extraction

• Planned Extrcapsular Cataract Extraction

• Phacoemulsification

• Femto Laser Assisted Cataract Surgery

Incision= stainless steel blade

• Paracentesis‐ tapered

• Two‐ step primary incision (2.7 mm internally)

• Visco‐ elastic

Capsulorhexis/Hydrodissection

• Disposable bent 21 gauge needle

• Disposable B.S.S cannula

Phacoemulsification

• Posterior polar exploration

(Howard Gimbel)

• Divide and conquer technique

(spatula assist)

Cortex Irrigation and Aspiration

• Sub‐incisional cortex removal‐ bi‐manual

• Aspiration via paracentesis 180 degrees from primary incision

• Irrigation via primary incision

Lens Implant Insertion

• Enlarge incision to 3mm

• Implantation into capsule bag

• Rotate trailing haptic to vertical

Complete Procedure

• Remove visco elastic

• I & A visco‐ elastic behind lens implant

• Hydrate Incision

Post‐ op Examination

• Portable slit lamp exam

• Instill Simbrinza

(thanks, Luther)

• Speak with patient and family

Lens Implant Exchange

• Intolerable unwanted optical image

Intracapsular Cataract Extraction

Conclusion

• Thanks for your attention

• Thanks for the honor to remember Dr. Lemoine

3/24/2016

1

Femtosecond laser assisted cataract extraction of posterior polar

cataracts

Chetan Soni, MD, FACS.

1

FL in posterior‐polar cataract surgery

• Surgical consideration in posterior polar cataract extractions

• Counseling (high risk of PCR, vitreous loss, dropped nucleus, retinal detachment, Nd:YAG capsulotomy)

• Surgical approach: Anterior

• Incision

• Viscoelastic ‐ cohesive

• Capsularrhexis ‐ optimum size between 4‐5 mm. Large capsularrhexismay not support sulcus fixated IOL, small may lead to difficulty in prolapsing nucleus if need be.




• Hydrodissection: best avoided

• Hydrodelineation: several authors recommend hydrodelineation as a good method to separate nucleus (Ref)

• Inside‐out delineation:




• Rotation: best avoided

• Division and fragment removal

• Epinucleus removal

• Pseudohole

• Cortex removal

• Posterior capsular polishing



• Surgical approach: Posterior

• plana lensectomy and vitrectomy

• interventional case series of 11 eyes of 8 patients.

• During a mean follow‐up of 13 months, 3 of 11 eyes developed posterior segment complications.



• Surgical approach: Posterior

• plana lensectomy and vitrectomy

• interventional case series of 11 eyes of 8 patients.

• During a mean follow‐up of 13 months, 3 of 11 eyes developed posterior segment complications.

3/24/2016

2

Femtodelineation

Technique first described by Dr. A. R. Vasavda(ref)

Surgical videos

Outcome of our 11 case series

Thank you.

Refractive Lens Exchange

Jason Stahl, MDDurrie VisionOverland Park, KS

Financial Disclosure• None

Refractive Lens Exchange

• 4 in 1 procedure• Distance Vision• Near Vision• Eliminates future cataract surgery• Stable Vision

Baby Boomers• Active lifestyle• Invest to improve quality of life• Do not want to wait for “cataract” surgery like parents did• Refractive surgery patient

• Enjoyed good uncorrected vision following vision correction surgery• Expect good uncorrected vision following RLE

• Distance and near

Patient Education• Why lens based surgery best option

• Dysfunctional Lens Syndrome• Effect on visual quality

• IOL options• Presbyopia-correcting• Blended vision (modified monovision)

• Ocular health• Patient lifestyle/visual needs• Appropriate expectations

Dysfunctional Lens Syndrome

Nuclear Sclerosis

Vision Correction

1. Change the corneal curvature

2. Exchange the lens


Stage 1 (mid 40’s – early 50’s)• Lens stiffens• Loss of ‘zoom’

DLS Stage 1 Surgical Options• LASIK/PRK: Blended Vision/Monovision• Corneal Inlays – Kamra• Refractive Lens Exchange for higher hyperopia


• Stage 2 (50’s-60’s)• Lens optics degrading

• Increasing lens haze• Yellow discoloration• Scatter of light

DLS Stage 2 Surgical Options• LASIK/PRK: Blended Vision/Monovision

• Educate patients

• Refractive Lens Exchange


• Stage 3 (60’s – 80’s)• Opacity of lens• Functional decline

DLS Stage 3 Surgical Options

•IOL Surgery

The Dysfunctional Lens

23 year old lens 48 year old lens 55 year old lensStage 1 DLS Stage 2 DLS

Stage 1 DLS: HD Analyzer Results

• Mid-normal OSI, MTF, and PSF.

• Good predicted VA

Stage 1 DLS: Densitometry• Mildly increased nuclear density

Stage 1 DLS: Slit Lamp Exam• Very mild “back scatter”

Stage 1 DLS Stage 2• Typically over 50 y/o• Loss of accommodation• Loss of visual quality

• Moderate OSI, PSF, and MTF• Good predicted VA• Recommend RLE

Stage 2 DLS: HD Analyzer Results

• Moderate OSI, PSF, and MTF

• Good predicted VA

Stage 2 DLS: Densitometry• Moderately increased nuclear density

Stage 2 DLS: Slit Lamp Exam• Moderately increased “back scatter”• Increasing yellow discoloration

Stage 2 DLS

Stage 3 DLS• Typically >65 but any age possible• Loss of accommodation and visual quality• Loss of visual acuity

• (BCVA and or glare testing<20/40)

• Poor OSI, MTF and predicted VA

• Recommend refractive cataract

Stage 3 DLS: HD Analyzer Results• Poor PSF• Poor MTF• Poor predicted VA• Moderate to poor

OSI

Stage 3 DLS Stage 3 DLS: Densitometry• Greatly increased nuclear density

Stage 3 DLS: Slit Lamp Exam• Greatly increased “back scatter.”• Yellow to brunescent discoloration• Cloudy appearance

Stage 3 OD and Stage 2 OS

Dysfunctional Lens Index Before and After Lens Surgery

Ocular Health

• Ocular issues to consider:• Dry Eyes – moderate/severe • Map-dot-fingerprint• S/P RK – corneal aberrations• S/P LASIK/PRK/CK – corneal aberrations• Fuch’s Dystrophy• Significant corneal scaring• PXE • Macular pathology (ARMD, ERM, DR)

Patient lifestyle and visual needs• Patient Questionnaire• Spend time talking to patient!• Occupation• Hobbies

Patient Expectations

• No guarantee that will be 100% spectacle free at all distances• Depends on IOL(s) used (combine IOLs)• Under-promise to exceed expectations• FDA clinical trials: 80% spectacle-free

• Quality of vision/Halos• Adaptation over time

• Functional near vision• “You will not have vision of a 20 year old”

IOL Options• Presbyopia-correcting IOLs

• Multifocal• Diffractive

• Central apodized optic: 2.5 D, 3 D and 4 D add (ReSTOR)• Full optic, non-apodized: 2.75 D, 3.25 D and 4 D add (Tecnis MTF)

• Accomodative• Crystalens (toric available)

• Combine (Mix and Match) to increase range of vision

• Pseudophakic monovision (blended vision)• Monofocal and Toric IOLs

Binocular UCVA-Distance

%

Binocular UCVA-Near (16 inches)

%

Defocus Curve - Monocular

Intermediate

Distance

Near

Defocus Curve - Binocular

Distance

Near

Intermediate

P<0.05

My (Simple) Approach:Quality > Range

• Dominant Eye• Tecnis One/Toric

• Target distance• Best image quality and quantity


• Non-Dominant Eye (2 options)• 1. Blended Vision

• Tecnis One/Toric• Target: -1.00 to -1.50 D (based on pupil size)• 80-90% spectacle free

• Occasional +1.00 D OTC readers and/or night driving glasses• Candidates

• Previous corneal refractive surgery• Corneal aberrations

• Small pupils• Increase depth of focus

• Concerned about visual quality


• Non-Dominant Eye (2 options)• 2. Multifocal

• Tecnis Multifocal • +2.75D, +3.25D or +4.0 D add

• 90% spectacle free• Occasional +1.00 to +1.50 D for intermediate tasks

• Candidates• Typically younger patient• Concerns about blended vision• Less concerns about visual quality

Extended Depth of Focus IOLs

• IOL Material• Single-piece hydrophobic acrylic

• Mask • PVDF & nano-particles of carbon• 1.36 mm aperture• 3.23 mm total diameter• 3200 microperforations• 6 microns thick

CE Marked IC-8™ IOL Design (Acufocus)Depth of Focus ComparisonOptical Modeling, 3.0 mm Pupil

IC-8™Small Aperture IOL Extended Depth of Focus (TC -0.75D)

Standard Mono-focal 0.0 D -0.5 D -1.0 D -1.5 D -2.0 D -2.5 D

20/50

20/40

20/3020/2020/10

20/50

20/40

20/3020/2020/10

20/50

20/40

20/3020/2020/10

46

Diffractive Bi-focal

0.0 D -0.5 D -1.0 D -1.5 D (66 cm)

-2.0 D(50 cm)

-2.5 D(40 cm)

0.0 D -0.5 D -1.0 D -1.5 D -2.0 D -2.5 D

• Defocus curve results from IC-8 IOL patients demonstrate broad range of vision across near, intermediate and far distances versus a monofocal IOL

• Mean post-op MRSE at their last follow-up was -0.14 D +/- 0.52

IC-8™ IOL Extends Depth of Focus

Data courtesy of Robert Ang, MD

-0.20-0.100.000.100.200.300.400.500.600.700.800.901.001.10

Acui

ty (L

ogM

AR)

Defocus Lens Power

Simulated Monofocal IOL Ang 6M (n=8)

Far Near

20/25

20/40

Tolerance to Uncorrected Astigmatism(IC-8™ Eyes vs. Monofocal Eyes)

• Cylinder defocus was done in 0.5 D steps, starting from manifest refraction. • Change in distance visual acuity compared to the visual acuity corrected at

manifest refraction at each cylinder defocus step was plotted against cylinder defocus steps

0

0.05

0.1

0.15

0.2

0.25

0.3-3-2.5-2-1.5-1-0.50

Cha

nge

in V

isua

l Acu

ity (

logM

AR)

Cylinder Defocus

Cylinder Defocus Curves IC-8 vs Monofocal

IC-8Monofocal

N=10

One line of loss

AMO Symfony• CE Mark• Currently in FDA Clinical trials

AMO Symfony

Tecnis Monofocal

Tecnis Multifocal

Tecnis Symfony

AMO Symfony Hit the Target• Refractive outcome optimized for best performance

• IOL calculations• Intraoperative aberrometry• Astigmatism correction – LRI vs Toric• Ocular surface• Correcting residual refractive error

• LASIK, PRK, LRIs• Yag capsulotomy

Conclusion• Dysfunctional Lens Syndrome

• Diagnostics help educate patients on need for lens-based refractive surgery

• Refractive Lens Exchange• 4 in 1 procedure• Patient education key – postop expectations• Future IOL options will improve visual range/quality

• Hit the Target• Refractive lens surgeon: you need to have all the tools• Refractive surgery patient expectations

Thank You

Macular Surgery in Uveitis

Sara Branson BS

Claudia Hooten, MD

Shree Kurup, MD

KU EyeCon 2016

Surgery in Uveitis

Fraught with risks

Timing is of essence

Generally in “good prognosis” patients

Avoid in active disease

No macular surgery in general

Lets discuss some real problems

TAKE HOME MESSAGE

There is value in surgery even in advancedsevere uveitis

Selection is key

Younger tend to be better

Macular edema still challenging

If possible, get it inactive

Case 1HPI

• 24 year‐old Caucasian female presents with bilateral panuveitis

• Hx of poor vision OU, recurrent red eyes and light sensitivity past 3 years

• Hx IVDU on suboxone

• Hx of oral ulcers and skin “blisters” on legs

• VA 20/200 OD and CF 4ft OS

• 2+Vitreous cell OD, +hypopyon OS with 3+vitreous cell

Fundus FA

FA OCT

Course Started oral prednisone 10mg PO daily, Valtrex 1g TID,

Levaquin 500mg PO BID, PF 1 gtts QID and atropine daily

Immune focused investigations were done, negative except HLA B51

Diagnosed with Behcets disease Japanese criteria “GOOSE”

She was ultimately treated with Cellcept, cyclosporine and low dose prednisone and she remained quiet after 1 year

VA 20/200 OD and 20/40 OS

Question? Would you consider vitrectomy and macular hole repair in the right eye?

Idiopathic Macular hole Prevalence ranges from 0.2‐3.3 per 1000

Bilateral MH incidence ranges from 5‐16%

Risk factors include age >65years and female gender

Pathogenesis: vitreomacular traction, contraction of premacular vitreous cortex, formation of foveal cyst

Macular hole stages Secondary Macular Hole Orbital trauma

High myopia

Uveitis (Behcets, Cat scratch, Fungal endophthalmitis, Syphilis, VKH)

Retinitis Pigmentosa

Stargardt disease

Alport syndrome

Best macular dystrophy

X linked Juvenile retinoschisis

Retinal arterial macroaneurysm

Laser induced maculopathy

Macular hole closure Idiopathic macular hole closure rate is 85% or more with use of PPV/ILM peel and gas or silicone tamponade

Spontaneous closure is less common

Secondary hole closure rate has lower rate

Due to larger hole size

Decreased retinal extensibility after retinal inflammation

Behcets Uveitis in Behcets is most frequently panuveitis

Macular edema is common and can get irreversible ischemia

Full thickness macular holes are uncommon and reported at 3.4%

Macular Hole in Behcets DiseaseHassan Al‐Dibhi et al

Sept 2011

Retrospective study of Behcets patients with MH from Jan 1998‐ Nov 2008

Of 159 patients, 21 eyes of 17 patients had MH

6 patients underwent PPV (2 had MH related RRD) only 1 hole closed

Surgical intervention did not result in significant visual improvement as compared to non‐operated eyes

EXCEPT for 1 patient who did not have macular ischemia

Pars plana vitrectomy with internal limiting membrane removal for a macular hole associated with Behçet's disease

T‐T Wu and M‐C Hong

Back to our patient Patient underwent PPV/membrane peel/C3F813% gas 6.12.15

OCT POM#1 and #2

Question?

Now her vision is 20/100 OD

How would you manage this patient now?

Observe vs re-operate?

She underwent second PPV/membrane peel/C3F813% gas 10.21.15

OCT at POM#120/80

Case 2: Sarcoidosis 20/100 from 1 yr ago 20/60 20/40 2 year prior Watch?

Compare

Post Op

MFC with intractable CME On TNF‐I Cellcept and CSA plus periodic Ozurdex: risk of CNV but persistent CME would destroy central macula.

BEFORE &AFTER SI OIL

References Gass JD. Idiopathic senile macular hole: Its early stages and pathogenesis. Arch Ophthalmol 1988;106:629‐

39.

Johnson RN, Gass JD. Idiopathic macular holes. Observations, stages of formation, and implications for surgical intervention. Ophthalmology 1988;95:917‐24.

Gass JD. Reappraisal of biomicroscopic classification of stages of development of a macular hole. Am JOphthalmol 1995;119:752‐9.

Spaide RF: Measurement of the posterior precortical vitreous pocket in fellow eyes with posterior vitreousdetachment and macular holes. Retina. 23:481‐485 2003

Privat E, Tadayoni R, Gaucher D, et al.: Residual defect in the foveal photoreceptor layer detected byoptical coherence tomography in eyes with spontaneously closed macular holes. Am J Ophthalmol.143:814‐819 2007

Criteria for diagnosis of Behçet′s disease. International Study Group for Behçet's Disease. Lancet. 1990;335:1078–80

Angioi‐Duprez K, Maalouf T, Gérin M, George JL. A full thickness macular hole as an uncommoncomplication of Behçet disease. J Fr Ophtalmol. 2001;24:172–4.

Sheu SJ1, Yang CA. Kaohsiung J Med Sci. 2004 Nov;20(11):558‐62. Macular hole in Behcet's disease.

RiskFactorsforIntraocularPressureElevationAfterDexamethasoneIntravitrealImplant

JulieQuick,MD,ResidentClassof2017PrimarySupervisor:PaulMunden,MD

Purpose:Intravitrealsteroidsarearecognizedcauseofincreasedintraocularpressure(IOP).Thegoalofthisstudywastoanalyzewhatriskfactorsareassociatedwiththedexamethasoneintravitrealimplant0.7mg(DEXimplant)andwhatmedicalandsurgicalinterventionswerenecessarytocontroltheIOP.

Methods:Aretrospective,descriptive,chartreviewwasperformedafterIRBapproval.AllpatientswhoreceivedaDEXimplantbyasingleretinalsurgeoninourdepartmentbetween2014and2016wereidentified.Ineachcase,genderandageofthepatients,diagnosis,numberofre‐interventionsandlateralitywereregistered.

Results:Outof48patients(60eyes)whoreceivedtheDEXimplant,13eyes(22%)hadanIOPelevation>5mmHgfrombaseline.Onaverage,peakIOPwas6weeksafterinjection.Eighteyes(62%)withIOPelevationwereadequatelycontrolledwithanaverageoftwoIOPloweringdrops;4eyes(30%)requiredfilteringsurgeryand1eye(8%)didnotrequireintervention,astheIOPwas<21mmHg.ThemostcommondiagnosisassociatedwithelevatedIOPwasposterioruveitis(30%)followedbyDME(27%),BRVO(18.8%)andCRVO(12.5%).Ninepatientshadahistoryofprimaryopenangleglaucoma(POAG).Ofthesepatients,3hadanIOPelevation>5mmHg.TwoofthesepatientswerenottakingIOPloweringmedicationsatthetimeoftheirinjection.The6patientswhodidnothaveanIOPelevationwerealreadyoneitheranIOPloweringdroporhadahistoryofglaucomasurgery.All4patientswithaknownhistoryofincreasedIOPaftertopicalsteroidshadanIOPelevationafterDEXimplant.

Conclusions:ThemajorityofpatientswhohadanelevatedIOPafterDEXimplantwerecontrolledwithIOPloweringmedications.Ahistoryofglaucomathatisuntreated,posterioruveitis,DME,andhistoryofsteroidresponsearepotentialriskfactorsforIOPelevationandshouldbemonitoredclosely.

PatternDystrophy:CaseSeriesLukeDolezal,MD,Resident,Classof2018PrimarySupervisor:AjaySingh,MD

Patterndystrophiesareagroupofmaculardiseasescharacterizedbyvariouspatternsofpigment

depositionandlipofuscinaccumulationwithinthemaculaduetoRPEdysfunction.Patternsmay

fluctuateinindividualpatientsovertimeandmaydifferbetweeneyes.Diseaseonsetistypicallyin

the5th‐6thdecade.Theyhavearelativelygoodvisualprognosis,althoughslowprogressivecentral

visionlossmayoccur,includingseverevisionlossinupto50%ofpatientsafterage70,dueto

chorioretinalatrophyand/orCNV.Patientsdiagnosedatanolderagemaybemisdiagnosedas

havingagerelatedmaculardegeneration,duetoasimilarfundusappearance.Accuratediagnosis

isimportanttoavoidunnecessarytreatmentandpatientanxiety.

ThispresentationwillreviewcasesofPatternDystrophyseenatKUEyeClinic.Wewilldiscuss

clinicalfeaturesandmultimodalimagingusedinthediagnosisandmonitoringofthesepatients.

A Neural Perspective on Diabetic Retinopathy

Rithwick Rajagopal, M.D., Ph.D.Assistant Professor

Department of Ophthalmology and Visual SciencesWashington University School of Medicine

April 9, 2016No financial disclosures

Early events in diabetic retinopathy

• Histologic and electron micrographic findings

Clinical features of diabetic retinopathy

• Mild to severe• Progressive (requires passage through intermediate stages)• Exclusively vascular features

A Current View of DR Progression

DM

Elevated glucose

Microvascular Damage;Inflammation;

Loss of Endothelial Integrity

MicroaneurysmsHemorrhages

Macular EdemaIschemia

Proliferation

VEGF

Other assays of visual function

• Multi-focal ERG• Measures of contrast sensitivity• Perimetry

Clinical evidence for neuro-retinal dysfunction in diabetes

• Electroretinography in patients with no evidence of retinopathy• Aggregate data suggest inner retinal pathology• Amplitude and kinetics of b-waves, oscillatory potentials

Prospective clinical trials

An Alternative Model for DR Progression

DM

Neuroretinal Damage

ClassicRetinopathy

Dysregulated insulin signaling;

Elevated glucose Neuro-inflammation;

Loss of Neurovascular

Coupling

Visible Microvascular

Defects

Development of a relevant animal model

• High-fat diet induces obesity and diabetes in mice (as in humans)• Progressive weight gain, adiposity and insulin resistance• Initial hyperinsulinemia, followed by relative hypoinsulinemia

Detection of retinopathy in rodents

• Trypsin-digest analysis of retinal microvasculature• Capillary leakage assays• Detection of retinal inflammatory mediators

Rodent electroretinography

• Full-field studies under anesthesia• Analysis of a-waves and b-waves• Oscillatory potentials• Association with disease severity

Metabolic stress induces neuro-inflammation

• Hijacking a system designed for defense against bacteria• Robust retinal inflammation occurs early in disease• May be more prominent in the inner retina• A potential early therapeutic target

Stages of Diabetic Retinopathy in the Type 2 Diabetes Mouse

• Neuro-inflammatory• Neuro-retinal• Microvascular

• Disease progresses slowly through these stages, allowing for controlled studies

Retinopathy Progression in the HFD Mouse:Lessons Learned

1. Metabolic disease is relatively mild, and retinopathy takes time to manifest!

2. Disease occurs in stages, and inner retinal dysfunction occurs early

3. This pattern is consistent with human disease

Future Directions

• Analysis of amacrine cells, bipolar cells and ganglion cells.• Screening for changes in gene expression, metabolites and lipids • Manipulation of signaling pathways in the retina

Acknowledgements

Clay Semenkovich, MDSheng ZhangLi YinXiaochao Wei, PhDLarry Spears, PhD

Peter Lukasiewicz, PhDGreg Bligard

WUSTL DOVS Core LabsAnne Hennig, PhDBelinda DanaGuanyi Ling

FundingHorncrest Foundation

K08-EY-025269P30-EY-002687

Research to Prevent Blindness

Contact: [email protected] // Referrals: 314-362-EYES

Tear Osmolarity in Diabetic Patients

Michelle Boyce, MD, Resident, Class of 2016 Primary Supervisor: Ajay Singh, MD

Diabetes Mellitus is a prevalent condition in the United States with many associated ophthalmic complications, including diabetic retinopathy and ocular surface disease. Studies have shown ocular surface disease is more common in the diabetic population than the general population.1,2 Diabetic patients have been shown to have a multitude of ocular surface irregularities that lead to the morbidity associated with ocular surface disease. Studies of diabetic patients have demonstrated changes in tear osmolarity,3 tear film instability,2,4 decreased reflex tearing,5 decreased corneal sensation,6,7 and loss of goblet cells.4,5 Deceased corneal sensation and the resultant decrease in sensory input to the autonomic nerves of the lacrimal gland may lead to reduced basal and reflex tear secretion.8-10 Additionally, studies have shown that panretinal photocoagulation (PRP) used in the treatment of proliferative diabetic retinopathy may alter the corneal subbasal nerve plexus11,12 and corneal sensitivity.6,13,14 Prior studies have shown variable results when assessing if diabetes disease severity markers can be correlated to the presence and severity of ocular surface disease.3,15,16

Common clinical testing for diagnosis and management of ocular surface disease includes tear break-up time (TBUT), Schirmer testing for tear production, staining of the cornea and conjunctiva, and tear osmolarity. Tear osmolarity is regarded as a hallmark of dry eye and has been shown to be the single best marker for diagnosis and classification of dry eye.17,18

Our study objectives were to determine if tear osmolarity in diabetic patients could be correlated to markers of diabetes severity, such as duration of disease, severity of diabetic retinopathy, history of requiring treatment by PRP, and history of nephropathy or neuropathy. Additionally, we examined the effects that PRP had on symptoms of ocular surface disease and tear osmolarity. Results of the research provides insight into the course of ocular surface disease in diabetics, particularly those patients with proliferative diabetic retinopathy requiring PRP, and allows us to better treat the morbidity associated with these conditions.

References: 1. Kaiserman I, Kaiserman N, Nakar S, Vinker S. Dry eye in diabetic patients. American Journal of

Ophthalmology. Mar 2005;139(3):498-503. 2. Inoue K, Kato S, Ohara C, Numaga J, Amano S, Oshika T. Ocular and systemic factors relevant to

diabetic keratoepitheliopathy. Cornea. Nov 2001;20(8):798-801. 3. Sagdik HM, Ugurbas SH, Can M, et al. Tear film osmolarity in patients with diabetes mellitus.

Ophthalmic Research. 2013;50(1):1-5. 4. Dogru M, Katakami C, Inoue M. Tear function and ocular surface changes in noninsulin-dependent

diabetes mellitus. Ophthalmology. Mar 200:108(3):586-592. 5. Goebbels M. Tear secretion and tear film function in insulin dependent diabetics. The British Journal

of Ophthalmology. Jan 2000;84(1):19-21.

Tear Osmolarity in Diabetic Patients, continued:

6. Rogell GD. Corneal hypesthesia and retinopathy in diabetes mellitus. Ophthalmology. Mar1980;87(3);229-233.

7. Rosenberg ME, Tervo TM, Immonen IJ, Muller LJ, Gronhagen-Riska C, Vesaluoma MH. Corneal structureand sensitivity in type I diabetes mellitus. Investigative Ophthalmology & Visual Science. Sep2000;41(10):2915-2921.

8. Parra A, Madrid R, Echevarria D, et al. Ocular surface wetness is regulated by TRPM8-dependent coldthermoreceptors of the cornea. Nature Medicine. Dec 2010;16(12):1396-1399.

9. Acosta MC, Peral A, Luna C, Pintor J, Belmonte C, Gallar J. Tear secretion induced by selectivestimulation of corneal and conjunctival sensory nerves. Investigative Ophthalmology & Visual Science.Jul 2004;45(7):2333-2336.

10. Cousen P, Cackett P, Bennett H, Swa K, Dhillon B. Tear production and corneal sensitivity in diabetes.Journal of Diabetes and its Complications. Nov-Dec 2007;21(6):371-373.

11. De Cilla S, Ranno S, Carini E, et al. Corneal subbasal nerve changes in patients with diabeticretinopathy: an in vivo confocal study. Investigative Ophthalmology & Visual Science. Nov2009;50(11):5155-5158.

12. Misra S, Ahn HN, Craig JP, Pradhan M, Patel DV, McGhee CN. Effect of panretinal photocoagulation oncorneal sensation and the corneal subbasal nerve plexus in diabetes mellitus. InvestigativeOphthalmology & Visual Science. Jul 2013;54(7):4485-4490.

13. Schiodte SN, Effects on choroidal nerves after panretinal xenon arc and argon laser photocoagulation.Acta Ophthalmol. Apr 1984;62(2):244-255.

14. Ruben ST. Corneal sensation in insulin dependent and non-insulin dependent diabetics withproliferative retinopathy. Acta Ophthalmol. Oct 1994:72(5):576-580.

15. Fuerst N, Langelier N, Massaro-Giordano M, et al. Tear osmolarity and dry eye symptoms in diabetics.Clinical ophthalmology. 2014;8:507-515.

16. Najafi L, Malek M, Valojerdi AE, et al. Dry eye and its correlation to diabetes microvascularcomplications in people with type 2 diabetes mellitus. Journal of diabetes and its complications. Sep-Oct2013;27(5):459-462.

17. Methodologies to diagnose and monitor dry eye disease: report of the Diagnostic MethodologySubcommittee of the International Dry Eye WorkShop (2007). The Ocular Surface. Apr 2007;5(2):108- 152.

18. Lemp MA, Bron AJ, Baudouin C, et al. Tear osmolarity in the diagnosis and management of dry eyedisease. American Journal of Ophthalmology. May 2011;151(5):792-798 e791.

UPDATE ON DIABETIC RETINOPATHY AND DME

MANAGEMENTKansas Eye Con 2016

April 8 & 9, 2016

Natalia Villate, M.D.

DISCLOSURE

• Dr Villate has no conflict of interest regarding this presentation

• Fort Lauderdale Eye Institute is currently enrolling patients in Industry-sponsored clinical trials and is also a participating center for the DRCR network. DrVillate is co-investigator in all current trials at FLEI.

• Genentech and Regeneron provided original slides of clinical trial results used in this presentation

• 1. OCT

• 2.AntiVEGF drugs for AMD

• The use of anti VEGF therapy for CNV and

wet macular degeneration has helped reduce the

vision loss by 41% and blindness by 46%.

(JAMA Ophthalmol, 2014;132(4):456-463.

MAYOR CHANGES IN LAST DECADE

HYPERGLYCEMIA

GLUCOSE SORBITOL

ALDOSE REDUCTASE

OSMOTIC DAMAGE

Lens changes

NADPH NADP

PERICYTE DAMAGE

AGE RAGE

APOPTOSIS

NEURODEGENERATION

ENDOTHELIAL CELL

DYSFUNCTION

INFLAMMATION

DIA

BE

TIC

R

ET

INO

PA

TH

Y

References: 1. Funatsu H, et al. Graefes Arch Clin Exp Ophthalmol. 2005;243:3-8. 2. Ma W, et al. Invest Ophthalmol Vis Sci. 2007;48:1355-1361. 3. Chung AS, Ferarra N. Annu Rev Cell Dev Biol. 2011;27:563-584. 4.Zhang W, et al. Immunotherapy. 2011;3:609-628. 5. Aiello LP, Wong JS. Kidney Int. 2000;58(suppl 77):S113-S119.

ROLE OF VEGF IN EYE DISEASE

• Elevated intraocular VEGF levels are a

major driver of neovascularization,

leakage, and macular edema—all of which can result in vision loss2-5

• In the eye, overexpression of VEGF is

associated with DME, wAMD, and

macular edema following RVO1-3

11

• In 2010, 25.6 million people

≥20 years old in the US had

diabetes1

• 11.3% of the population1

• By 2020, prevalence is

expected to rise to 15% of

adults in the US (39 million)2

DIABETES PREVALENCE IN THE US

1. Centers for Disease Control and Prevention Website. National Diabetes Fact Sheet, 2011.http://www.cdc.gov/diabetes/pubs/factsheet11.htm. Accessed May 18, 2012.

2. UnitedHealth® Center for Health Reform and Modernization. Working Paper 5, 2010.http://www.unitedhealthgroup.com/hrm/UNH_WorkingPaper5.pdf. Accessed June 23, 2012.

3. Centers for Disease Control and Prevention Website. Diabetes Data & Trends. 2009. http://apps.nccd.cdc.gov/DDT_STRS2/NationalDiabetesPrevalenceEstimates.aspx. Accessed May 18, 2012.

2009 Estimates of the Percentage of Adults ≥20 Years Old With Diagnosed Diabetes3

Age-adjusted percent

0 - 6.3

6.4 - 7.5

7.6 - 8.8

8.9 - 10.5

> 10.6

References: 1. Xu L, et al. Invest Ophthalmol Vis Sci. 2013;54:1616-1624. 2. Chakravarthy U, et al; IVAN Study Investigators. Ophthalmology. 2012;119:1399-1411.

Patients can reduce

the risk and severity

of DME by controlling

their ABCs6,7:

•A1c

•Blood pressure

•Cholesterol

MICRO- AND MACROVASCULAR COMORBIDITIES IN PATIENTS WITH DIABETES1-5

28.5% Diabetic retinopathy (DR)in patients 40 years of age or older

13.6% Diabetic macular edema (DME) in patients with DR

9.1% Strokein patients 35 years of age or older

21.9% Coronary heart disease*in patients 35 years of age or older

29.9% Diabetic nephropathyin diabetes patients

≈60% to 70% Diabetic neuropathyin diabetes patients

References: 1. Diabetes statistics. American Diabetes Association website. http://www.diabetes.org/diabetes-basics/diabetes-statistics/?loc=DropDownDB-stats. Published January 26, 2011. Accessed June 21, 2012. 2.National diabetes fact sheet: national estimates and general information on diabetes and prediabetes in the United States, 2011. Centers for Disease Control and Prevention website. http://www.cdc.gov/diabetes/pubs/pdf/ndfs_2011.pdf. Accessed October 22, 2013. 3. Varma R, et al. Poster presented at: 2012 Joint Meeting of the American Academy of Ophthalmology and Asia-Pacific Academy of Ophthalmology; November 10-13, 2012; Chicago, IL. Poster PO252. 4. Diabetes data & trends. Centers for Disease Control and Prevention website. http://www.cdc.gov/diabetes/statistics/cvd/fig2.htm. Updated November 6, 2012. Accessed October 22, 2013. 5. United States Renal Data System. http://www.usrds.org/atlas.aspx. Accessed February 7, 2013. 6. National Eye Institute, National Institutes of Health. NIH Publication No. 2642. 7. Ciulla TA, et al. Diabetes Care. 2003;26:2653-2664.

• 40%–50% of diabetic patients do not receive recommended eye care1

• Joslin study of patient self-awareness of DR2

• At their first study visit, 83% of patients with DR and 78% with vision-threatening DR were unaware that they had the disease

• 50% with vision-threatening DR did not have timely follow-up eye exams

MAJORITY REMAIN UNDIAGNOSED OR UNTREATED

Modified, with permission, from the American Academy of Ophthalmology Retina Panel. Preferred Practice Pattern® Guidelines, Diabetic Retinopathy. San Francisco, CA: American Academy of Ophthalmology; 2008. Available at www.aao.org/ppp

1. Healthcare Effectiveness Data and Information Set Report (HEDIS) 2011. http://www.sanfordhealthplan.org/ClassLibrary/Page/Images/files/HEDIS_Report_2011.pdf. Accessed May 30, 2012.2. Soliman et al. ARVO, 2011 abstract.

Diabetes Type Recommended Timefor First Examination

Recommended Follow-up

Type 1 3–5 years after diagnosis Yearly

Type 2 At time of diagnosis Yearly

American Academy of Ophthalmology: Recommended Eye Examination Schedule (Including Dilated Eye Exam) for Diabetic Patients

ETDRS

• Overall, decreased moderate visual loss by ~ 50%

• Treated group 13%

• Control group 22%

ETDRS Report #1 Arch Ophthalmol 103:1796-806, 1985

Mod

erat

e vi

sual

loss

ETDRS• ETDRS – how often was there improvement?

• Only 3% had > 3 lines of improvement

• Only 17% had any improvement in vision after 5 years

• Vision improvement depends where you start

• Only 114 treated eyes had vision ≤ 20/40

• 640 treated eyes (85%) had vision better than 20/40

• Of those that could gain three lines (start with baseline vision of 20/40 or

worse) how many gained three or more lines in the ETDRS?

• About 40%

• About how much treatment to expect?

- Quarterly visits. Three to five lasers over one to two years

SO WHAT IS NEW

• Add anti VEGF to laser or possibly replace laser.

• Use Steroids to treat inflammatory component of

retinopathy

• Medical management matters more than many

of us realize.

HOW DOES ANTI VEGF MEDICATIONS AFFECT DIABETIC RETINOPATHY?

RIDE AND RISE - STUDY DESIGN RIDE/RISE

Objective: Evaluate efficacy and safety of intravitreal RANIBIZUMAB compared with sham injections in patients with center-involved DME

1:1:1 Randomization (one eye per subject)

Screening: BCVA 20/40 to 20/320, OCT CST ≥275 μm

Sham Injection(n=257)a

RANIBIZUMAB 0.3 mg(n=250)a,b

24-Month Controlled Treatment Period (monthly intravitreal/sham injections; macular laser, if eligible, beginning month 3)

RANIBIZUMAB 0.5 mg (n=252)a

Month 24

Month 36

DME

Primary Endpoint

Long-term Open-label Extension With 0.5 mg LUCENTIS

Monthly RANIBIZUMAB 0.5 mg

Monthly RANIBIZUMAB 0.3

mgb

Monthly RANIBIZUMAB 0.5

mg

aPooled RIDE and RISE enrollment.Nguyen et al. Ophthalmology. 2012;119:789.

RANIBIZUMAB is approved for a 0.3-mg dose in DME

≥15 ETDRS LETTERS FROM BASELINE AT MONTH 24 (PRIMARY ENDPOINT)

RIDE/RISE

aCochran-Mantel-Haenszel chi-squared test (stratified). The LOCF imputation method was used. Vertical bars are 95% confidence intervals. Reported percentages and differences vs sham are unadjusted, test and P value are adjusted for baseline VA (≤55, >55 letters), baseline HbA1c (≤8%, >8%), and prior treatment for DME (yes, no). LUCENTIS FDA Briefing Book.

Sham(n=257)

0.3 mg(n=250)

Pe

rce

nt

of

su

bje

cts

= 24.0 (P<0.0001)a

Pooled RIDE and RISE

Percentages of patients who lost ≥15 letters from baseline at month 24 (secondary endpoint)

LUCENTIS 0.3 mg: 2.0%Sham: 9.3%

MACULAR AND PANRETINAL LASER TREATMENT THROUGH MONTH 24

RIDE/RISE

aExploratory endpoint. Adjusted difference vs sham was: -34.4% for the 0.3-mg group; P<0.0001 for LUCENTIS groups vs sham (Cochran-Mantel-Haenzel chi-squared test [stratified]). bP<0.0001 for all LUCENTIS groups vs sham (Wilcoxon test [stratified]). Beginning at month 3, patients were evaluated monthlyfor the need for rescue macular laser according to protocol-specific criteria: OCT CFT ≥250 μm with <50-μm change from prior month, no laser in prior3 months, and evaluating physician deems laser therapy to be beneficial. LUCENTIS FDA Briefing Book.

Outcome Measure

Pooled RIDE and RISE

Sham(n=257)

LUCENTIS0.3 mg (n=250)

Received macular lasera 72.0% 37.6%

Mean no. of treatmentsb 1.7 0.7

Received panretinal laser 11.7% 0.8%

• Aprox. 40% % gained ≥3 lines with monthly Ranibizumab 0.3 mg vs 15.2% in the sham group

• Rapid and sustained improvement in both vision and retinal anatomy as early as day 7

• Delayed treatment with Ranibizumab (after month 24) in patients originally randomized to sham did not result in the same extent of improvement seen in patients treated with Ranibizumab from the outset

• Majority of Ranibizumab-treated patients did not receive any protocol-specified laser treatment, while almost half of sham patients received 2 or more laser treatments

• Patients treated with Ranibizumab showed improvement in the severity of retinopathy

KEY FINDINGS RIDE/RISE

*After 5 initial monthly doses

VIVID and VISTA:Study Design

Patients randomized 1:1:1

Primary Endpoint:Week 52

Primary endpoint: Mean change in BCVA

Key Secondary endpoints Change in OCT

Change in Diabetic Retinopathy Severity Scale

(DRSS)

Continued treatment through Year 3

Randomized, multicenter, double-masked trials in patients with clinically significant DME with central involvement and ETDRS BCVA 20/40 to 20/320

N=406 (VIVID) N=466 (VISTA)

IVT Aflibercept2 mg q8 wks*

IVT Aflibercept2 mg q4 wks

Laser Photocoagulation

Proportion of Patients Gaining≥10 and ≥15 Letters at Week 100

PRIMARY ENDPOINT

Compared with baseline; last observation carried forward.VIVID FAS: Laser: n=132; IAI 2q4: n=136; IAI 2q8: n=135; VISTA FAS: Laser: n=154; IAI 2q4: n=154; IAI 2q8: n=151.

Pro

po

rtio

n o

f p

ati

ents

0%

20%

40%

60%

80%

100%

25.0%

12.1%

27.9%

13.0%

58.1%

38.2%

63.6%

38.3%

49.6%

31.1%

59.6%

33.1%

Laser

IAI 2q4

IAI 2q8

≥15 letters≥10 letters

≥15 letters≥10 letters

VIVID VISTA

The proportion of patients loosing >15 letters was aprox 11% (9.7% and 12.9%) in the laser group and less than 3% in the aflibercept treated groups (2.2% and 3.2% in IAI 2q4 and 1.5% and 0.7% in IAI 2q8)

-250

-200

-150

-100

-50

00 4 8 12 16 20 24 28 32 36 40 44 48 52 56 60 64 68 72 76 80 84 88 92 96 100

-250

-200

-150

-100

-50

0

Week

µm

Mean Change in Central RetinalThickness Through Week 100

SECONDARY ENDPOINT

-84 Laser

-191* IAI 2q4-191* IAI 2q8

-196 IAI 2q8-212 IAI 2q4

-86 Laser

-73

-186*-183*

-195*-192*

-66

Central subfield; SD-OCT.VIVID FAS: Laser: n=132; IAI 2q4: n=136; IAI 2q8: n=135. VISTA FAS: Laser: n=154; IAI 2q4: n=154; IAI 2q8: n=151.

VIVID

VISTA

*P<0.0001 vs laser

0%

20%

40%

60%

80%

100%

8.2%15.6%

29.3%

37.0%32.6%

37.1%

Laser

IAI 2q4

IAI 2q8

In VISTA, analyses were performed using the FAS. In VIVID, analyses included only evaluable patients defined as those with a gradable baseline DRSS and a post-baseline DRSS score.Compared with baseline; last observation carried forwardDRSS, Diabetic Retinopathy Severity Score

P<0.0001 2q4 vs laserP<0.0001 2q8 vs laser

154 151154

P=0.0004 2q4 vs laserP<0.0001 2q8 vs laser

82 8685

Proportion of Patients With ≥ 2 StepImprovement in DRSS at Week 100

SECONDARY ENDPOINT

VIVID VISTA

Pro

po

rtio

n o

f p

ati

ents

KEY FINDINGS

• Aflibercept was as effective as Ramibizumab at improving vision in

aprox 40% of treated patients

• Treatement every 8 weeks was almost as effective as monthly

treatements ( after dose loading period)

• Anatomic response was significantly better in patients treated with

Aflibercept than in laser patients

• Independent of the treatement interval,approximately 1/3 of

Aflibercept treated patients showed improvement in the severity of

the retinopathy

DRCR NETWORK COMPLETED PROTOCOLS

23

Protocol # of Subjects

I: Laser-Ranibizumab-Triamcinolone Study for DME 691

J: Laser-Ranibizumab-Triamcinolone Study for DME + PRP 333

K: The Course of Response to Focal Photocoagulation for DME 128

L: Autorefraction and E-ETDRS Measurements in DME 490

N: Intravitreal Ranibizumab for Vitreous Hemorrhage from PDR Study 261

O: Comparison of Time Domain OCT & Spectral Domain OCT in DME 1183

P: Pilot Study of Individuals with DME Undergoing Cataract Surgery 68

Q: Individuals with Diabetes without DME Undergoing Cataract Surgery 317

R: NSAIDs in Eyes with Non Central Involved DME 125

S: Prompt PRP vs. Ranibizumab + Deferred PRP for DPR* 305

T: Anti-VEGF comparison* 660

DRCR NETWORK ONGOING PROTOCOLS

Protocol # of Subjects

M: Diabetes Education Study* 1875

U: Phase II Persistent DME Study**

V: Very Good Visual Acuity** 39

Genetics Ancillary Study: Genes in Diabetic Retinopathy** 855

DRCR Network Participant Total Since 2003 8807

* Enrollment done/in active follow-up; **Recruiting

THE DIABETIC RETINOPATHY CLINICAL RESEARCH NETWORK

5-Year Follow-up of a Randomized Trial Evaluating Ranibizumab Plus Prompt versus Deferred Laser for

Diabetic Macular Edema

PROTOCOL I

PROTOCOL I MAIN OUTCOMES• Number of visits at 5 years:

• 38 in the ranibizumab + Prompt Laser (13-8-7-5-4)

• 40 in the Ranibizumab + deferred laser (13-10-8-6-5)

Median of Injections at 5 years

• 13 in the ranibizumab + Prompt Laser (8-2-1-0-0)

• 17 in the Ranibizumab + deferred laser (9-3-2-1-0)

Additional Laser treatements needed at 5 years

• All received laser in the ranibizumab + Prompt Laser

• Less than 50% needed laser in the Ranibizumab + deferred laser

Percentage of patients with vision improvement > 15 ETDRS letters at 5 yeasr

• 27% in the ranibizumab + Prompt Laser

• 38% in the Ranibizumab + deferred laser

CHANGE IN VA OVER 5 YEARSSTRATIFIED BY BASELINE VA

27• Test for interaction at 5 Year time point: P = 0.001• Test for interaction from longitudinal model: P = 0.004

MEAN CHANGE IN VISUAL ACUITY AT FOLLOW-UP VISITS AMONG EYES THAT WERE PSEUDOPHAKIC AT BASELINE*

28Visit Week

* Values that were ±30 letters were assigned a value of 30

29

STEP CHANGES OF IMPROVEMENT/WORSENING IN DIABETIC RETINOPATHY BY BASELINE SEVERITY

Change from baseline to 1-year visit*

Sham

+Prompt

Laser

Ranibizumab

+Prompt

Laser or Deferred Laser

Triamcinolone

+Prompt

Laser

Baseline Severity: Moderately Severe NPDR or Better

N = 150 N = 182 N = 80

Improved by ≥2 levels 4% 25% 25%

Worsened by ≥2 levels 7% 3% 3%

P value for comparison with Sham

P = 0.08 P =0.17

Baseline Severity: Severe NPDR or worse

N = 83 N = 121 N = 70

Improved by ≥2 levels 19% 28% 13%

Worsened by ≥2 levels 8% 1% 3%

P value for comparison with Sham

P = 0.03 P = 0.17

*Photos were missing or ungradeable for 61 eyes in the sham+prompt laser group, 72 eyes in the ranibizumab groups, and 33 eyes in the triamcinolone+prompt laser group

PROTOCOL I KEY FINDINGS

• VA gain at 1 year was maintained to 5 years concomitant with diminishing

need for treatment over time

• Adding laser at initiation of ranibizumab was no better than deferring

laser at least 24 weeks

• Deferring laser may be associated with more VA gain through 5 years,

especially in eyes with worse VA at baseline

• Eyes assigned to prompt laser needed fewer injections over 5 years

• Few eyes in either group had substantial VA loss

• About 1/3 still thickened more work to be done

• Consider IVTA for subjects pseudophakic at baseline30

WHAT ABOUT RANIBIZUMAB ALONE?

Ophthalmology. 2010;117:2146-51. Epub 2010 Sep 19.

Two-year outcomes of the ranibizumab for edema of the mAcula in diabetes (READ-2) study.

READ 2 THREE YEAR OUTCOMES

Ophthalmology. 2010;117:2146-51. Epub 2010 Sep 19.Two-year outcomes of the ranibizumab for edema of the mAcula in diabetes (READ-2) study.

-1.6 letters -36μm

+2.0 letters 24 μm

Mean number of injections

2.3p=0.08

5.4

3.3 p=.11

READ-2 CONFIRMED --THE RESTORE STUDY

Mitchell P, Bandello, F, Schmidt-Erfurth U, et al. The

RESTORE study: Ranibizumab monotherapy or combined

with laser versus laser monotherapy for diabetic macular

edema. Ophthalmology 2011;118:615–25.

RESTORE

RBZ

RBZ + Laser

Laser alone

--The Restore Study: Ranibizumab monotherapy or combined with laser versus laser monotherapy for diabetic macular Edema Ophthalmology 2011;118:615–25.

HOW ABOUT AVASTIN?PACORES and BOLT

PACORES

J. F. Arevalo, J. G. Sanchez, L. Wu et al., “Primary intravitreal bevacizumab for diffuse diabetic macular edema. The Pan-American Collaborative Retina Study Group at 24 months,”Ophthalmology, vol. 116, no. 8, pp. 1488–1497.e1, 2009.

Real-World Results With Bevacizumab for DME Doesn't Match Trial ResultsArevalo et al. Br J Ophthalmol 2016.

BOLT

• A prospective randomized trial of intravitreal bevacizumab or laser therapy in the management of diabetic macular edema (BOLT study) 12-month data: report 2.

• Michaelides, et al, Ophthalmology. 2010 Jun;117:1078-1086.e2.

• 80 eyes randomized to laser

vs. bevacizumab.

• The bevacizumab group

gained a median of 8 ETDRS

letters, whereas the laser

group lost a median of 0.5

ETDRS letters (P = 0.0002).

Meta-analysis and review on the effect of bevacizumab in diabetic macular edema.Goyal, et. al., Graefes Arch Clin Exp Ophthalmol. 2011;249:15-27.

HOW DO ANTI VEGF AGENTS COMPARE?

DIABETIC RETINOPATHY CLINICAL RESEARCH NETWORK

Aflibercept, Bevacizumab, or

Ranibizumab for DME: Two-year ResultsPROTOCOL T

Supported through a cooperative agreement from the

National Eye Institute; National Institute of Diabetes and Digestive and Kidney Diseases; National Institutes of Health,

Department of Health and Human Services EY14231, EY14229, EY018817

DME TREATMENT: ANTI-VEGF(COMPLETERS OF THE GIVEN VISIT ONLY)

40

Aflibercept Bevacizumab Ranibizumab‡Global P-Value

# of Injections: Median (25th, 75th percentile)

Year 1 9 (8, 11) 10 (8, 12) 10 (8, 11) 0.045†

Year 2 5 (2, 7) 6 (2, 9) 6 (2, 9) 0.32

Over 2 Years 15 (11, 17) 16 (12, 20) 15 (11, 19) 0.08

NOTE: 98% of protocol required re-injections were given over 2 years † Pairwise comparisons (adjusted for multiple comparisons): A-B: P = 0.045, A-R: P = 0.19, B-R: P = 0.22.‡Seven study eyes received 1 injection and 2 eyes received 2 injections of 0.5-mg of ranibizumab prior to the FDA approving a 0.3 –mg dosage of ranibizumab for DME treatment and protocol revision to use 0.3-mg dose

DME TREATMENT: LASER(COMPLETERS OF THE GIVEN VISIT ONLY)

41

Aflibercept Bevacizumab RanibizumabGlobal

P-Value

At least one focal/grid laser

Year 1 37% 56% 46% <0.001*

Year 2 20% 31% 27% 0.046‡

Over 2 Years 41% 64% 52% <0.001†

*Pairwise comparisons (adjusted for multiple comparisons): A-B: P<0.001, A-R: P=0.06, B-R: P=0.06‡ Pairwise comparisons (adjusted for multiple comparisons): A-B: P=0.046, A-R: P=0.12, B-R: P=0.37. †Pairwise comparisons (adjusted for multiple comparisons): A-B: P<0.001, A-R: P=0.04, B-R: P=0.01.

SUBGROUP ANALYSIS 1 YEAR RESULS

0 8 16 24 32 40 48Visit Week

20/50 or worse

+19+14

+12

0

5

10

15

20

0 8 16 24 32 40 48

Mea

n Chan

ge is Visual Acuity

Letter Score

Visit Week

20/32-20/40

~+8

Aflibercept Bevacizumab Ranibizumab

≥15 LETTER IMPROVEMENT AT 2 YEARS

20% 17% 19%

Pe

rce

nt

Observed Data

* P-values adjusted for baseline visual acuity and multiple comparisons

*P 0.89

58%52% 55%

Pe

rce

nt

Observed Data

20/32 – 20/40 20/50 or wose

*P 0.75

POST HOC ANALYSIS OF APTC ADVERSE EVENTS STRATIFIED BY PRIOR MI/STROKE

44

% of pts with at least one event

Aflibercept Bevacizumab Ranibizumab

No Prior MI/Stroke

N = 203 N = 193 N = 193

Non-fatal MI 3% 2% 2%

Non-fatal stroke <1% 3% 3%

Vascular death <1% 2% 4%Any APTC Event 5% 6% 9%

Prior MI/Stroke N = 21 N = 25 N = 25

Non-fatal MI 5% 0 8%

Non-fatal stroke 0 4% 20%

Vascular death 5% 16% 8%

Any APTC Event 10% 20% 36%Global P-value adjusting prior myocardial infarction, prior stroke: P = 0.06.

KEY FINDINGS PROTOCOL T2 YEAR RESULTS

VA gains in all three drugs at 2 years, with reduced number of

injections and lasers in year 2

With MILD initial VA loss little difference in visual acuity.

At worse levels of initial visual acuity aflibercept more effective at

improving visual acuity versus bevacizumab, but not ranibizumab.

Pre-defined systemic APTC rates were higher in the

ranibizumab group, not seen in previous clinical trials (outlier)

45

WHAT ABOUT PRP?

PROTOCOL SPrompt PRP

vs. Ranibizumab + Deferred PRP

for PDR Study

PRIMARY QUESTION

• Is visual acuity using ranibizumab for PDR not worse than

treatment with PRP at 2 years?

Non-inferiority margin of 5 letter

SECONDARY QUESTION

• Are there potential benefits of ranibizumab on:

Vision throughout follow-up (area under the curve)

Peripheral vision

Macular edema

Incidence of vitrectomy

MEAN CHANGE IN VISUAL ACUITYAREA UNDER THE CURVE ANALYSIS

48

Area under the curve (AUC) analysis: Pre-planned secondary outcome

-5

0

5

10

15

0 16 32 52 68 84 104

Mea

n V

isual

Acu

ity C

han

ge

(Let

ter

Sco

re)

Visit Week

Ranibizumab Group PRP Group

N = 191N = 203

+ 4.5

-0.3

Adjusted Mean Difference over 2 years (AUC): +4.2 P-value<0.00195% Confidence Interval: (+3.0, +5.4)

N = 168N = 160

49

0 16 32 52 68 84 104Visit Week

Without “Baseline DME”

-4-202468

101214

0 16 32 52 68 84 104

Mea

n V

isual

Acu

ity C

han

ge(L

ette

r Sco

re)

Visit Week

With “Baseline DME”

Ranibizumab Group PRP Group

+2

+7.9

- 0.5

+1.8

N = 42 N = 33 N = 147

N = 46 N = 37 N = 155 N = 130N = 126

*Outlying values were truncated to 3 SD from the mean

Mean Change in Visual AcuityStratified by Baseline DME

Mean Change in Visual AcuityStratified by Baseline DME

PERIPHERAL VISUAL FIELD OUTCOMES2-YEAR VISIT

50

Humphrey Visual Field 30-2 + 60-4

RanibizumabGroup

(N = 58)

PRPGroup

(N = 57)Cumulative Point Score Change from Baseline

Mean -23 -422

Difference (P-Value) 372 dB (P<0.001)

Mean Deviation Change from Baseline

Mean -0.08 -2.50

Difference (P-Value) 2.2 (P< 0.001)

PROPORTION OF EYES DEVELOPING CENTER INVOLVED DME WITH VISION IMPAIRMENT

(EYES WITHOUT BASELINE DME AND VISION IMPAIRMENT)

51

2-Year Adjusted Difference: 19% 95% Confidence Interval: (10% to 28%)P-value < 0.001

N = 155

N = 147

KEY FINDINGS PROTOCOL S

PRP remains effective for PDR in 21st century

Ranibizumab for PDR is a as good as PRP for VA at 2 years

Ranibizumab is an alternative to PRP for PDR

No substantial safety concerns for at least 2 years

May be the preferred initial treatment for some patients

PDR and DME but cost, follow-up compliance, and

patient preference need to be considered

• Longer follow-up needed to determine if effect is sustained

through 5 years 52

WHAT ABOUT STEROIDS?

STEROIDS FOR DME: AVAILABLE MOLECULES

Triamcinolone acetonide (FDA approved for

GCA,SO,Uveitis)

• Triescence: Off label for DME

Dexamethasone Implant Ozurdex™

Fluocinolone acetonide Ivuvien™,

Safety concerns

cataract

Glaucoma

Other

• MEAD: (n=148) Treatement-naïve patients with DME, BCVA of 20/50

to 20/200 and CRT of ≥300 (OZURDEX) vs sham. 3 year results:

• 19.5% gained ≥3-lines vs 10.7% overall

• Pseudophakic patients: 20% vs 11%

• Cataract formation 65% vs 20.4% in sham group

• Increases in IOP usually controlled with medication or no therapy;

• 2 patients (0.6%) in the DEX implant 0.7 mg group and 1 (0.3%) in

the DEX implant 0.35 mg group required trabeculectomy.

STEROIDS FOR DME: CLINICAL TRIALS

Ophthalmology. 2014 Oct;121(10):1904-14. doi: 10.1016/j.ophtha.2014.04.024. Epub 2014 Jun 4.Three-year, randomized, sham-controlled trial of dexamethasone intravitreal implant in patients with diabetic macular edema.Boyer DS, Yoon YH, Belfort R Jr, Bandello F, Maturi RK, Augustin AJ, Li XY, Cui H, Hashad Y, Whitcup SM; Ozurdex MEAD Study Group

STEROIDS FOR DME: CLINICAL TRIALS

• FAME: (n=956) persistent DME despite treatment with

available therapies. Primary endpoint=VA gain≥15 letters at 24

months.

• 3-year results: ~30% improved ≥ 3 lines from baseline (17% in

control group)

• 75% had 1 ILUVIEN implant over 3 years

• ≥30 mmHg IOP rise in 18.4%

• 5% rate of incisional glaucoma surgery (4.8-8.%)

• 81.7% developed cataract at month 36 (80% had CE)

STEROIDS: RATIONALE FOR CLINICAL USE

• Aprox 1/3 of patients do not respond or have an incomplete response to

Anti VEGF therapy regardless of agent

• Predominantly VEGF-mediated disease

• benefit form AntiVEGF agents

• Non-predominantly VEGF-mediated disease

• partial or no benefit from AntiVEGF combination therapy

• Side effect profile

• Phakic vs pseudophakic status may lead us to switch earlier of later in

the treatment process

10/24/2014OD 20/100 s/p Avastin x 3

560µ637µ

66 yo ♂, phakic. NIDDM diagnosed in May 2014. Metformin/Glipizide/LisinoprilInitial eye exam Severe NPDR with DME A1C 9%

10/24/2014OS 20/100 s/p Avastin x 3

67 yo ♂, phakic. 1 year later (11/04/2015) A1C 6.9%

OD: 20/60 (3 line gain)163 µ decrease CFTs/p 11 Injections (6L 5 E)s/p 1 Focal laser

OS: 20/60 (3 line gain)170 µ decrease CFTs/p 12 Injections (7L 5 E)s/p 1 Focal laser

67 yo ♂, phakic. 5 months later (3/09/2016) A1C 6.8%

OD: 20/50 (4 line gain)59µ decrease CFT (Total 222µ)s/p IVT and Ozurdex (1/20/16)Total 13 injections

OS: 20/50 (4 line gain)154µ decrease CFT (Total324 µ)s/p IVT and Ozurdex (2/20/16)Total 14 injections

BUT, THERE MAY BE INCREASED COSTS …

Economic considerations of macular edema therapies.

Smiddy WE.Ophthalmology. 2011 Sep;118:1827-33.

DO NOT FORGET LASER

The course of response to focal/grid photocoagulation for diabetic macular edema.

Diabetic Retinopathy Clinical Research Network. Retina. 2009;29:1436-43.

DRCR Prospective study of 122 eyes with center-involved diabetic macular edema.

At 16 weeks, about 50% had a decrease in CST by > or =10% compared with baseline

23% to 63% continue to improve without additional treatment.Laser effect slow and steady, might eventually allow fewer visits

and injections.

WHAT ABOUT SYSTEMIC DIABETES CONTROL?

FIBRATES AND STATINS: FIELD STUDY FIELD (OPHTHALMOLOGY SUB STUDY)

• ETDRS photos performed on 1012 subjects

PRIMARY OUTCOME

• Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study designed to assess the effect of fenofibrate on cardiovascular events (N~10,000).

• Fenofibrate did not significantly reduce the risk of the primary outcome of coronary events.

SECONDARY OUTCOME

• 30% reduction (p=0.003) in need for a first laser therapy with fenofibrate compared to placebo.

Lancet 2005; 366: 1849–61 • Lancet, 2007: 370, 1687-1697.

ACTION TO CONTROL CARDIOVASCULAR RISK IN DIABETES ACCORD TRIAL

• Studied effects of intensive glucose

control on cardiovascular endpoints

in type 2 diabetes.

• Similar to DCCT in type 1 diabetes.

• ~10,000 subjects

- ~3,000 participated in the eye

substudy.

Hgb A1C

the use of intensive therapy to target normal glycated hemoglobin levels for 3.5 years increased mortality.

Supplement to: The ACCORD Study Group and ACCORD Eye Study Group. Effects of medical therapies on retinopathy progression in type 2 diabetes. N Engl J Med 2010;363:233-44. DOI: 10.1056/NEJMoa1001288.

ACTION TO CONTROL CARDIOVASCULAR RISK IN DIABETES ACCORD TRIAL

• Triglycerides reduced • Effect on retinopathy progression

Supplement to: The ACCORD Study Group and ACCORD Eye Study Group. Effects of medical therapies on retinopathy progression in type 2 diabetes. N Engl J Med 2010;363:233-44. DOI: 10.1056/NEJMoa1001288.

WHAT ABOUT EDUCATION?

Effect of Diabetes EducationDuring Retinal Ophthalmology Visits

on Diabetes Control(Protocol M)

Thank You

The microvascular pathology of diabetic retinopathy

Rithwick Rajagopal, M.D., Ph.D.Assistant Professor

Department of Ophthalmology and Visual SciencesWashington University School of Medicine

April 9, 2016No financial disclosures

Worldwide Rates of Diabetic Retinopathy

1. Increasing in the United States, although visual impairment rates are on decline

2. Rapid (and disproportionate) global increases in this disease

3. Many populations will not have resources to treat vision loss, as it is treated in wealthier nations

Current treatments for microvascular disease due to diabetes

1. Glucose control (with glycated hemoglobin being the endpoint).

2. VEGF antagonism

3. Laser

4. Corticosteroids

The Transformative Effect of VEGF Antagonism

1. Review of relevant clinical trials

2. Comparative efficacy

3. Safety concerns

The role of VEGF in maintenance of healthy retina

1. Overview of expression of VEGF and its receptors in the retina

2. Concerns for chronic antagonism

The “Glucose-Centric” Diabetic Retinopathy Hypothesis

DM

Elevated glucose

Microvascular Damage;Inflammation;

Loss of Endothelial Integrity

MicroaneurysmsHemorrhages

Macular EdemaIschemia

Proliferation

VEGF

Is Glucose Really the Primary Culprit Causing Diabetic Microvasculopathy?

1. Use caution when interpreting data from clinical trials (DCCT, EDIC, UKPDS)

2. Lessons from previous glucose metabolism pathway-targeted therapy (PKC-DRS, Sorbinil trials)

1. Can we intervene at earlier stages of disease?

2. Can we do so in a more cost-effective manner?

Two Undersold Studies in Ophthalmology

1. Fenofibrate Intervention and Event Lowering in Diabetes (FIELD)• Multicenter study based in Australia• Does use of fenofibrate reduce retinopathy?

2. Action to Control Cardiovascular Risk in Diabetes (ACCORD)• U.S.-based multicenter trial• Also assessed effect of fenofibrate on

microvascular disease

What are the Obstacles to Using Fenofibrate for Diabetic Retinopathy?

1. Adverse effects

2. Questions about its mechanism of action

How Does Fenofibrate Protect the Retina in Diabetes?

1. What are the effects (or lack of) on serum lipids?

2. Direct actions in the retina through transcriptional regulation

3. Modification of retinal lipid environment

4. Anti-inflammatory actions

What Molecules are Altered in the Retina with Fenofibrate Therapy?

1. Screening for candidates

2. Validation of putative targets

AcknowledgementsClay Semenkovich, MD

Sheng ZhangLi YinXiaochao Wei, PhDLarry Spears, PhD

FundingHorncrest Foundation

K08-EY-025269P30-EY-002687

Research to Prevent Blindness

Contact: [email protected] // Referrals: 314-362-EYES

Washington University Retina ServiceP. Kumar Rao, MDRajendra Apte, MD, PhDStanford Taylor, MD

DOVS Core LabsAnne Hennig, PhDBelinda DanaGuanyi Ling

Effects of Simulated Afferent Pupillary Defect on Automated Perimetry Robert Null, MD, Resident, Class of 2017 Primary Supervisor: Paul Munden, MD

Glaucoma is a progressive optic neuropathy characterized by known patterns of vision loss. Functional

testing of visual fields through automated perimetry allows the clinician to monitor for glaucoma

progression. Predictive threshold models, most notably the Swedish Interactive Thresholding Algorithm

(SITA) have been developed to speed testing time, and judicious statistical analysis of field data can provide

insights into rate of disease progression and efficacy of treatment. However, it is less well understood how

these statistical models behave when other etiologies of vision loss are introduced. To further investigate

the behavior of these models, otherwise healthy subjects participated in at 24-2 SITA fast automated visual

field in the dominant eye. Fields were tested with and without the presence of 0.9 neutral density (ND)

filter to simulate a non-specific, quantifiable, generalized visual depression. Statistical parameters

commonly utilized to assess glaucoma severity and progression, including mean deviation, pattern

deviation, and visual field index (VFI), were compared between filtered and non-filtered fields, with

significant trends reported in detail in the accompanying presentation. Vision loss from glaucoma does not

occur in a clinical vacuum and better understanding of commonly used statistical metrics under non-ideal

conditions will aid the clinician in the assessment and management of this complex disease.

Detecting Functional Change in Progressing Glaucoma: Visual Field Guided Progression Analysis (GPA) Paul Munden, MD Associate Professor, KU Eye Glaucoma – A characteristic optic neuropathy associated with multiple conditions and usually associated with a higher than normal intraocular pressure. Diagnosis based on characteristic changes in optic nerve:

Structure Clinical examination Concentric enlargement of ON cup Increased vertical C/D ratio Focal notching and thinning at superior/inferior poles ISNT Disc hemorrhages Excavation NFL defects Zone beta peripapillary atrophy ON and NFL OCT Loss of peripapillary NFL thickness ISNT Function Automated Visual Fields Characteristic NFL associated loss Initiate Treatment - Consider IOP goal

Medical Laser Surgical

Verify IOP at goal Monitor for progression CPM if stable Alter or increase therapy if IOP above goal or progression noted

Detecting Functional Change in Progressing Glaucoma: Visual Field Guided Progression Analysis (GPA), continued: Glaucoma progresses treated or untreated! Can lead to visual disability and blindness Important to be able to detect progression and modify IOP goal and therapy How do we detect progressive glaucoma? Structural changes from baseline Serial Disc photographs In OHT majority of patients converted to glaucoma on the basis of ON changes Progressive glaucoma Serial Optic Nerve OCT

Patients with progressive NFL thinning had progressive visual field loss by three different VF progression criteria

Glaucoma Diagnosis

Set IOP Goal

Initiate and Optimize Therapy

Monitor IOP Disc Photos ON OCT Automated VF

Stable

Confirm Progression

Add or Alter Therapy

Progression

Reset GPA Baseline Fields

Detecting Functional Change in Progressing Glaucoma: Visual Field Guided Progression Analysis (GPA), continued: Functional changes from baseline Serial automated visual fields Difficult to assess actual functional progression examining serial automated visual fields We compare the most recent field to the one before or maybe the first field Interpretation can be challenging!

Long term and short term fluctuation OHTS 86% of initial abnormal VF had subsequent normal field 66% of those with two abnormal fields had subsequent normal field 12% of those with three abnormal fields had subsequent normal field CNTG as many as 4 to 6 abnormal fields necessary to confirm progression Test-retest variability of perimetry results depend on many factors

Frequency of seeing curve Scotoma depth and location Overall visual field status Less variability with very good or very bad fields Test strategy used Full Threshold, SITA Standard, SITA Fast Patient Experience

Learning effect External factors Inexperienced technicians Room temperature Chair comfort Patient physical limitations “Bad Hair” day Is there a tool to help us discern actual functional progression from artifact? Guided (Glaucoma) Progression Analysis Software package for Humphrey Field Analyzer

Designed to identify and quantify statistically significant visual field loss progression for glaucoma patients Two tests designated as baseline. Up to 14 follow-up tests may be compared to the averaged baseline examinations Identifies progression when testing results fall outside the expected range of test-retest variability

GPA Normative database 363 subjects 9 sites world-wide

Detecting Functional Change in Progressing Glaucoma: Visual Field Guided Progression Analysis (GPA), continued:

Mild to severe glaucoma First time test takers excluded 4 clinic visits in 1 month, 3 fields per visit Full Threshold, SITA Standard, SITA Fast

Event Analysis An event that is a statistically significant (“real”) change from baseline

Evaluating each individual point in central field for test-retest variability in pattern deviation value Filters out changes in overall height of hill of vision Differentiates between localized glaucoma damage and effect of cataract or pupil size EMGT event criteria: 3 consecutive visual fields with contain three or more identical points that have changed at a statistically significant level from baseline

Trend Analysis Rate of change of Visual Field Index (VFI) over time Regression analysis of slope of line Statistical analysis to determine slope is “real” vs fluctuation within expected limits

Rate of Progression and visual trend of progression pattern plotted graphically.

Using GPA Software activation Set up Print Out options Choosing Baseline Fields Two oldest automatically chosen unless Learning effect False Positives of 15% or more Choose new Baseline fields after change in therapy or identification of learning effect

Compares subsequent fields with baseline fields with statistical analysis Statistical evaluation of effectiveness of therapy in slowing or stopping progression Baseline – Follow-up Configurations SITA Standard F/U Exam must have SITA Standard of Full Threshold Baseline

Exams SITA Fast F/U Exam must have SITA Fast or Full Threshold Baseline Exams May have 30-2 and 24-2 Exams in the same analysis Does not support FastPac or Central 10-2 for Baseline or F/U

GPA Reports

GPA Summary Report Baseline fields with grayscale and key indices at top VFI plot and VFI bar in center

Detecting Functional Change in Progressing Glaucoma: Visual Field Guided Progression Analysis (GPA), continued: Current visual field with grayscale and indices at bottom Progression Analysis Probability Plot and GPA alert at bottom Single Field Analysis with GPA Standard Single Field Analysis with grayscale and usual indices Separate box for GPA info and Progression Analysis Probability plot No VFI plot or linear regression analysis Full GPA report The whole ball of wax Baseline page with grayscale and indices including VFI plot All follow-up exams (up to 14) with Progression Probability Analysis and GPA alert GPA Last 3 Follow-up Full GPA lite Baseline page and three most recent follow-up exams Interpreting GPA Reports Deviation from Baseline Plot

Compares pattern deviation of follow-up test to average of pattern deviation of baseline tests

Progression Analysis Probability Plot Denotes statistical significance of the dB changes shown in deviation plot Evaluates point by point Weighted toward center points Single dot – point not changing by statistically significant amount Open triangle- at least 5% greater deterioration from expected Average of 2-3 points (out of 76) by chance alone Not uncommon in glaucoma patients

Half-filled triangle – statistically significant deterioration at that point in 2 consecutive tests Solid triangle - statistically significant deterioration at that point in 3 consecutive tests X – data out of range for analysis. GPA cannot determine if deviation at that point statistically significant Usually in areas where defect already very deep or absolute

GPA Alert Alerts to deterioration in consecutive tests Applies to the whole field, not individual points

Detecting Functional Change in Progressing Glaucoma: Visual Field Guided Progression Analysis (GPA), continued:

No Progression Detected Possible Progression – statistically significant deterioration in 3 or more points on two consecutive tests Likely Progression – statistically significant deterioration in 3 or more points on three consecutive tests

VFI Plot

Graphs VFI values of included exams as a function of patient’s age Linear regression analysis of VFI over time At least 5 exams over 2 years Not drawn when slope positive (learning effect) Not drawn when 95% confidence level on slope is greater than 5% VFI Bar – histogram indicates current VFI value and will graphically indicate the 2 to 5 year projection of the linear progression line. Clinical Interpretation

GPA Software is a statistical analysis software not a replacement for clinical observation and physician interpretation Aid in analysis of data - does not make clinical judgment How does it compare to the “experts” when calling progression? “Level of agreement between majority expert consensus of subjective determination of visual field progression and GPA is “fair.” In cases of disagreement with GPA, the expert consensus was usually progression. Access to GPA results after initial classification changed expert consensus in 11 of 100 cases.” Tanna, Budenz, et al, Ophthalmology. 2012 March; 119(3):468-473 Garbage in – Garbage Out Inspect the printout Assess the triangles Check the defect depth, location, contiguous, anatomic (RNFL) pattern Possible Progression Likely Progression Correlate with other examination findings! If progression, check progression fields for reliability Reset Baseline fields following intervention for progression

KU MD and Residency Alumni

Wayne Anliker MD MD Class: 1997 Emporia, KS

Adam AufderHeide MD Residency Class: 2014 Mission, KS

Douglas B. Babel MD MD Class: 1992 Residency Class: 1997 Erie, PA

Hasan Bahrani MD Residency Class: 2009 Houston, TX

Richard Barr MD MD Class: 1957 Residency Class: 1964 Overland Park, KS

Donald E. Beahm MD MD Class: 1971 Great Bend, KS

William R. Beck MD MD Class: 1983 Newton, KS

Deloris W. Bell MD MD Class: 1968 Residency Class: 1972 Overland Park, KS

Ravi B. Berger MD Residency Class: 2006 Cleveland, OH

Anna Berry MD Residency Class: 2016 Prairie Village, KS

Ann Bidwell MD MD Class: 1980 Round Lake, IL

Miranda Bishara MD Residency Class: 2010 Prairie Village, KS

Thomas C. Black MD Residency Class: 1968 Kansas City, MO

Audrey Blacklock MD MD Class: 2006 Liberty, MO

Jeffrey A. Boomer MD MD Class: 2001 Wichita, KS

Michelle Boyce MD Residency Class: 2016 Prairie Village, KS

Lance Brown MD Residency Class: 2001 Joplin, MO

Emily Broxterman MD Residency Class: 2015 Kansas City, MO

Michael Brusco MD Residency Class: 2011 Kalamazoo, MI

Trey M. Butler MD Residency Class: 1993 Joplin, MO

Anita Campbell MD MD Class: 2010 Residency Class: 2014 Wichita, KS

William Campbell MD MD Class: 1965 Ottawa, KS

Thomas P. Campbell MD Residency Class: 1986 Wheat Ridge, CO

Patrick K. Canon MD Residency Class: 2001 Colorado Springs, CO

Timothy Cavanaugh MD MD Class: 1986 Residency Class: 1990 Overland Park, KS

Mary Champion MD Residency Class: 2015 Phoenix, AZ

Ryan Christensen MD MD Class: 2004 (Wichita) Residency Class: 2008 Shawnee Mission, KS

Amy Ciccio MD MD Class: 2002 Residency Class: 2006 Kansas City, MO

Justin T. Cohen MD Residency Class: 1977 Wheat Ridge, CO

Brian E. Conner MD MD Class: 1972 Salina, KS

Terry A. Cox MD MD Class: 1975 Residency Class: 1979 Columbia, SC

KU MD and Residency Alumni Charles H. Cozean MD MD Class: 1962 Residency Class: 1966 Cape Girardeau, MO

Valerie Crandall MD Residency Class: 1982 Ft. Myers, FL

Terrence Curran MD MD Class: 1972 Residency Class: 1977 Prairie Village, KS Mohammad Dastjerdi MD Residency Class: 2013 Newark, NJ Sujote David MD MD Class: 1991 Residency Class: 1994 Kansas City, KS Brandon Davis MD Residency Class: 2007 New Orleans, LA John Doane MD MD Class: 1990 Residency Class: 1995 Leawood, KS Luke Dolezal MD Residency Class: 2018 Prairie Village, KS Thomas G. Duckett MD MD Class: 1967 Broomfield, CA Alina Dumitrescu MD Residency Class: 2015 Iowa City, IA

David S. Dyer MD MD Class: 1989 Overland Park, KS

Richard J. Eggleston MD Residency Class: 1974 Clarkston, WA Mark D. Emig MD MD Class: 1988 Residency Class: 1993 Omaha, NE Nicholoas Engelbrecht MD MD Class: 1996 St. Louis, MO

Richard Falter MD MD Class: 1967 Hutchinson, KS Cynthia A. Ferreira MD Residency Class: 2005 Reno, NV Michael Floyd MD Resdency Class: 2010 Bloomington, MN Michael Foote MD Residency Class: 2002 El Paso, TX

Charles R. Ford MD MD Class: 1963 Shawnee, KS

John Frangie MD MD Class: 1987 Greenfield, MA

Kenneth J. Frank MD MD Class: 1992 Ottawa, KS

Eric L. Fry MD MD Class: 2003 Residency Class: 2007 Garden City, KS Luther L. Fry MD MD Class: 1967 Garden City, KS

Scott Fudemberg MD Residency Class: 2007 Philadelphia, PA Valerie Garden MD Fellow: 2000 Santa Rosa, CA

Amy Gemperli MD MD Class: 1992 Residency Class: 1996 Kansas City, MO Darrell E. Genstler MD Residency Class: 1981 Albany, OR James A. Gessler MD MD Class: 1974 Springfield, MO Erin Gilliland MD MD Class: 1999 St. Joseph, MO William A. Godfrey MD MD Class: 1965 Residency Class: 1971 Prairie Village, KS Robert T. Goetzinger MD MD Class: 1971 Residency Class: 1976 Riverdale, GA

KU MD and Residency Alumni Andre J. Golina MD Residency Class: 1979 West Palm Beach, FL Charles E. Graham MD Residency Class: 1993 Las Vegas, NV R. Bruce Grene MD MD Class: 1978 Wichita, KS Hasan Hakim MD Residency Class: 1997 Dearborn, MI James R. Hardin MD Residency Class: 1997 Salisbury, NC Wilmer Harms MD MD Class: 1956 North Newton, KS Toby Hartong MD Residency Class: 1982 Leawood, KS James D. Haug MD MD Class: 1981 Residency Class: 1985 Atchinson, KS K. Dwight Hendricks MD Residency Class: 1983 Kansas City, KS James A. Hiatt MD MD Class: 1999 Residency Class: 2003 Mesa, AZ

Derek Horkey MD Residency Class: 2017 Prairie Village, KS

Alan Hromas MD Residency Class: 2014 Houston, TX

Ana G. Huaman MD MD Class: 1984 Residency Class: 1996 Albuquerque, NM Quentin C. Huerter MD MD Class: 1959 Residency Class: 1969 Leawood, KS Denise A. Hug MD MD Class: 1996 Kansas City, MO John D. Hunkeler MD MD Class: 1967 Residency Class: 1973 Overland Park, KS Joel Hunter MD Fellow: 2010 Orlando, FL Richard L. Irwin MD MD Class: 1975 Residency Class: 1980 Putnam, CT Srinivas Iyengar MD Residency Class: 2008 Littleton, CO Randolph Jackson MD Residency Class: 2004 Kansas City, KS

Russell Jayne MD Fellow: 1997 Las Vegas, NV Andrew J. Jefferson MD Residency Class: 1986 Leawood, KS Faisal Jehan MD MD Class: 1998 Residency Class: 2003 Fontana, CA Cindi Kalin Johnson MD Residency Class: 1994 Leavenworth, KS Josh Jones MD Residency Class: 2018 Prairie Village, KS Raymond E. Kandt MD Residency Class: 1967 Prairie Village, KS Neda Karimi MD MD Class: 2001 Residency Class: 2005 Santa Monica, CA Rickey D. Kellerman MD MD Class: 1978 Wichita, KS Daniel M. King MD MD Class: 1974 Residency Class: 1982 Red Bluff, CA David A. Kingrey MD MD Class: 1994 Wichita, KS

KU MD and Residency Alumni Jess Koons MD MD Class: 1957 Liberal, KS Ernest Kovarik MD Residency Class: 1969 Shawnee Mission, KS Randall J. Kresie MD MD Class: 1984 Residency Class: 1988 Topeka, KS Kartik Kumar MD Residency Class: 2011 Houston, TX Leila Kump MD Residency Class: 2010 Gaithersburg, MD Bradley R. Kwapiszeski MD MD Class: 1991 Shawnee Mission, KS Brian A. LaGreca MD Residency Class: 1992 Billings, MT Dale Laird MD MD Class: 1968 Residency Class: 1974 Belton, MO Ryan Larscheid MD Residency Class: 1974 Fountain Valley, CA Diana Lind DO Residency Class: 1997 Kearney, NE

Timothy Lindquist MD Residency Class: 2012 Overland Park, KS Rebecca Linquist MD Residency Class: 2013 Rapid City, SD Robert A. Lowenthal MD Residency Class: 1994 Springfield, IL Barry C. Malloy MD Residency Class: 1989 Wyomissing, PA Babak Marefat MD MD Class: 1999 Topeka, KS John Marsh MD MD Class: 1992 Residency Class: 1996 Topeka, KS Federico Mattioli MD Residency Class: 2000 Houston, TX Donald Maxwell MD Residency Class: 1986 Oklahoma City, OK Mark Mazow MD Residency Class: 1990 Dallas, TX Thomas L. McDonald MD MD Class: 1984 Residency Class: 1988 Hays, KS

Lynne G. McElhinney MD MD Class: 1995 Kansas City, MO

Wilber McElroy MD MD Class: 1961 Topeka, KS

Frank E. McKee MD MD Class: 1970 Overland Park, KS Peter Mitrev MD Residency Class: 1998 Chesapeake, VA Reid Mollman MD Residency Class: 2018 Prairie Village, KS

Louis Monaco DO DO Class: 1982 Clinton, MO Susan K. Mosier MD MD Class: 1995 Lawrence, KS

Everett C. Moulton MD Residency Class: 1979 Ft. Smith, AR

Andrew Moyes MD MD Class: 1989 Kansas City, MO Brian C. Mulrooney MD Residency Class: 1999 Huntsville, AL Forrest P. Murphy MD MD Class: 1978 Residency Class: 1985 La Jolla, CA

KU MD and Residency Alumni Todd Nickel DO DO Class: 2000 Residency Class: 2004 Tyler, TX Robert Null MD Residency Class: 2017 Prairie Village, KS Bruce B. Ochsner MD MD Class: 1965 Wichita, KS Sara O'Connell MD MD Class: 1994 Overland Park, KS Timothy Olsen MD MD Class: 1989 Atlanta, GA Lynn W. O'Neal MD MD Class: 1977 Lawrence, KS Richard A. Orchard MD MD Class: 1965 Lawrence, KS Charles F. Palmer MD Residency Class: 2000 Cheyenne, WY Theodore Pasquali MD Fellow: 2013 Lakewood, CA Michael Pekas MD Residency Class: 1976 Sioux Falls, SD

Cindy Penzler MD MD Class: 1985 Residency Class: 1989 Topeka, KS Ryan Pine MD Residency Class: 2012 Charleston, IL Kenneth C. Place MD MD Class: 1973 Prairie Village, KS John Pokorny MD MD Class: 1989 Hays, KS Patrick (Frank) Price MD MD Class: 1975 Blue Springs, MO Bradford S. Prokop MD Residency Class: 1961 Ft. Myers, FL Gary V. Puro MD Residency Class: 1975 Santa Fe, NM Anjulie Quick MD Residency Class: 2017 Prairie Village, KS Deborah Reid MD Fellow: 2000 Annapolis, MD John S. Reifschneider DO DO Class: 1981 Leavenworth, KS

Robert Reinecke MD MD Class: 1959 Philadelpha, PA Martin Reinke MD Residency Class: 1995 Southlake, TX Donald A. Relihan MD MD Class: 1954 Residency Class: 1957 Wichita, KS Garrick Rettele MD MD Class: 1991 Coffeyville, KS Michael G. Reynolds MD MD Class: 1988 Emporia, KS Geoffrey L. Rice MD Residency Class: 1985 Ukiah, CA

James R. Rinne MD MD Class; 1984 Residency Class: 1988 Campbellsville, KY

David S. Rothberg MD Residency Class: 1983 Palm Harbor, FL

John Rufe MD MD Class: 1950 Shawnee Mision, KS

Roland Sabates MD MD Class: 1973 Kansas City, MO

KU MD and Residency Alumni E. Michael Sarno MD Residency Class: 1981 West Des Moines, IA

Roger B. Schlemmer MD MD Class: 1968 Residency Class: 1973 Springfield, MO

Albert W.G. Schubert MD MD Class: 1974 Residency Class: 1977 Charleston, IL Perry Schuetz MD MD Class: 1971 Residency Class: 1975 Great Bend, KS

Michael Seligson MD MD Class: 1991 Santa Fe, NM My Le Shaw MD Residency Class: 2012 Linden, MI

C. Eric Shrader MD MD Class: 1978 Wichita, KS

Joseph N. Simone MD MD Class: 1983 Residency Class: 1987 Leawood, KS

C. Byron Smith MD Residency Class: 1980 Billings, MT

Wallace B. Smith MD MD Class: 1954 Residency Class: 1962 Lees Summit, MO

Ryan Smith MD Fellow: 2009 Augusta, GA

David L. Spalding MD MD Class: 1959 Residency Class: 1965 Rogersville, MO

Jennifer Spiegel MD MD Class: 2009 Residency Class: 2013 Thousand Oaks, CA

Erin D. Stahl MD Residency Class: 2009 Fellow: 2011 Kansas City, MO

Larry Stauffer MD MD Class: 1969 Residency Class: 1975 Jefferson City, MO

Ann Stechschulte MD Residency Class: 2005 Shawnee Mission, KS

Richard A. Stein MD Residency Class: 1994 Leavenworth, KS

Michael Stiles MD MD Class: 1985 Residency Class: 1989 Overland Park, KS

Carl Stout MD Residency Class: 1976 Independence, MO Timothy M. Stout MD MD Class: 1995 Residency Class: 1999 Leawood, KS

Manju Subramanian MD Residency Class: 2002 Boston, MA Beatty G. Suiter MD MD Class: 1999 Residency Class: 2004 Fellow: 2009 Shawnee Mission, KS Kevin Toller MD MD Class: 1994 Grove, OK Patricia L. Turner MD Residency Class: 1984 Reno, NV Chris Ullrich DO, FACS DO Class: 1992 Washington, MO Steven Unterman MD Residency Class: 1987 Prairie Village, KS Trent Vande Garde MD MD Class: 1995 Topeka, KS Michael P. Varenhorst MD Residency Class: 1984 Wichita, KS Natalia Villate MD Residency Class: 2008 Boca Raton, FL Them Vu MD MD Class: 2000 Plano, TX

KU MD and Residency Alumni Brian Boxer Wacher MD Fellow: 1998 Los Angeles, CA Matthew Wayner MD Residency Class: 1990 Kerrville, TX Walter Dan Weaver MD MD Class: 1969 Residency Class: 1973 Topeka, KS Gary Weiner MD MD Class: 1990 Salina, KS Robert Weir MD Residency Class: 1967 Kansas City, MO Mark L. Wellemeyer MD MD Class: 1988 Wichita, KS Kent L. Wellish MD Residency Class: 1992 Las Vegas, NV Thomas J. Whittaker MD, JD MD Class: 1990 Prairie Village, KS Thomas Williams MD Residency Class: 1994 Hickory, NC Stewart M. Wilson MD MD Class: 1968 Residency Class: 1974 Roseburg, OR

Terria Winn MD MD Class: 1982 Wichita, KS Chauncey B. Witcraft MD Residency Class: 1984 Miami, OK Jerry B. Wurster MD MD Class: 1964 Residency Class: 1968 Scottsdale, AZ Lillian Yang MD Residency Class: 2016 Prairie Village, KS Michelle Yao MD Residency Class: 2009 Woodbury, NY

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