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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 dcotterman@akhcme.com.
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
Visual Field (VF) and Driving
31
Visual Field (VF) and Driving
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.
FL in posterior‐polar cataract surgery
• Surgical consideration in posterior polar cataract extractions
• Surgical approach: Anterior
• Hydrodissection: best avoided
• Hydrodelineation: several authors recommend hydrodelineation as a good method to separate nucleus (Ref)
• Inside‐out delineation:
FL in posterior‐polar cataract surgery
• Surgical consideration in posterior polar cataract extractions
• Surgical approach: Anterior
• Rotation: best avoided
• Division and fragment removal
• Epinucleus removal
• Pseudohole
• Cortex removal
• Posterior capsular polishing
FL in posterior‐polar cataract surgery
• Surgical consideration in posterior polar cataract extractions
• 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.
FL in posterior‐polar cataract surgery
• Surgical consideration in posterior polar cataract extractions
• 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
Dysfunctional Lens Syndrome
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
Dysfunctional Lens Syndrome
• 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
Dysfunctional Lens Syndrome
• 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
My (Simple) Approach:Quality > Range
• 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
My (Simple) Approach:Quality > Range
• 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: rajagopalr@vision.wustl.edu // 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: rajagopalr@vision.wustl.edu // 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
Contactinformation:
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