EyeCon. April 8 & 9, 2016 The Venue 4800 W 135 th St., Ste. 108 Leawood, KS 66209

Kansas EyeCon 2016 April 8 & 9, 2016 The Venue 4800 W 135 th St., Ste. 108 Leawood, KS 66209 Sponsored by the University of Kansas Department of Ophthalmology and the Lemoine Alumni Society

DEPARTMENT OF OPHTHALMOLOGY SCHOOL OF MEDICINE CLINICAL FACULTY 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 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

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

Kansas EyeCon 2016 We wish to acknowledge and sincerely thank these organizations for exhibiting at this conference: Platinum Sponsors: Alcon Laboratories, Inc. Ellex Enhanced Medical Services Heidelberg Engineering Regeneron Pharmaceuticals, Inc. Shire Medical Affairs Silver Sponsors: Allergan, Inc. Bio Tissue Carl Zeiss Meditec, Inc. Bronze Sponsor: KU Audio Reader Network

Kansas EyeCon 2016 The Venue 4800 W 135 th 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 cell arteritis; 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.

LEMOINE DISTINGUISHED ALUMNI LECTURERS LECTURER TITLE DATE Timothy W. Olsen, MD Rock Chalk Retina Talk: 100 year KU 5/9/2014 KU SOM MD 89 Luther L. Fry, MD Standard Cataract Surgery: Tips & Tricks 5/8/2015 KU SOM MD 67 Learned after 40,000+ Cases John D. Hunkeler, MD Continuous Education 4/8/2016 KU SOM MD 67 KU Eye Residency 73

Alumni Speakers Luther L. Fry, MD MD: 1967 John D. Hunkeler, MD MD: 1967; Residency: 1973 Natalia Villate, MD Residency: 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 Ophthalmology and 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

Temporal Artery Biopsy Outcomes in Patients with Suspected Giant Cell Arteritis Lillian Yang, MD, Resident, Class of 2016 Primary Supervisor: Jason Sokol, MD Giant cell arteritis (GCA) is a systemic disease that can have devastating ophthalmic consequences. The diagnosis is based on clinical characteristics and established by the presence of inflammatory markers. However, the only specific diagnostic test is a temporal artery biopsy (TAB). Although uncommon, complications related to TAB, such as postoperative hematoma, scalp necrosis, wound infection, damage to facial nerve, and drooping of eyebrow, can occur. Additionally, TAB as a diagnostic tool for GCA is not perfectly sensitive, with reported rates of 70 90%. This presentation is intended to review results from temporal artery biopsies performed at the University of Kansas Hospital and to determine their utility in diagnosing GCA.

Bilateral Orbital Myeloid Sarcoma in an Adult Patient with Recurrent Acute Myeloid Leukemia (AML) Reid Mollman, MD, Resident Class of 2018 Primary Supervisor: Jason Sokol, MD Objective: Here, we discuss a single case of Myeloid Sarcoma, also previously referred to as chloroma or granulocytic sarcoma, which manifested as bilateral orbital masses in an adult with recurrent AML. Method: Presentation of a single case of bilateral orbital Myeloid Sarcoma in an adult with recurrent AML. Results: The patient in this case presented with substantial proptosis and ophthalmoplegia secondary to large bilateral Myeloid Sarcoma orbital masses in the setting of recurrent AML. Six weeks after treatment with intrathecal chemotherapy, as well as radiation, the patient had virtually complete resolution of the orbital masses. Conclusion: This is an interesting and rare case, where an adult patient presented with bilateral orbital Myeloid Sarcoma. It is very rare for myeloid sarcoma to present in the orbit, and, making this case even rarer, is the presentation in an adult. Upon literature review, it appears that only approximately 20 cases of this nature have been described in the past two decades.

Recurrent Squamous Cell Carcinoma with Orbital Invasion (some requiring exenteration) in the Setting of Immunosuppression Following Organ Transplants Case Series Joshua Jones, MD, Resident Class of 2018 Primary Supervisor: Jason Sokol, MD Purpose: Review current literature on anti graft medication pharmacology and discuss the increased risk of squamous cell carcinoma in transplant patients, along with retrospectively reviewing cases in which transplant patients were treated by an interdisciplinary team, including Oculoplastics and Otolaryngology for squamous cell carcinoma with orbital involvement. Design: Charts were analyzed from four patients who underwent surgical resection, some radical, for treatment of squamous cell carcinoma following immunosuppressive therapy for transplants between 2011 and 2016, recording the association with the type of immunosuppressive medication and blood levels, extent of invasion of the tumors and type of procedure required for effective treatment. Setting: Ophthalmology Department at a university hospital setting Patients: Among the 4 patients included, average age was 62 years old; 2 were male and 2 were female. One patient was deceased at the time of retrospective review, due to metastatic disease. Each patient had a different type of transplant, such as heart, liver, kidney or bone marrow. The average time at initial diagnosis of squamous cell carcinoma was 6.3 years following initiation of anti graft medication. Conclusions: Squamous cell carcinoma is a significant cause of morbidity and mortality for patients on long term immunosuppression following otherwise successful transplants. In our series of 4 patients, 50% required lifesaving radical surgical resection, including exenteration. Even with a successful surgery, the rate of mortality is high, given the extent of invasion. Our findings confirm what other studies have shown: that these patients need to be monitored closely for signs of peri orbital malignancy and treatment should not be delayed, given the high rates of recurrence and tissue invasion.

Retrospective Review of Indications of Evisceration, Enucleation or Exenteration at one Academic Institution Derek Horkey, MD, Resident Class of 2017 Primary Supervisor: Jason Sokol, MD Purpose: At times in ophthalmology, instead of vision enhancing or vision preserving procedures, it is necessary to perform eye destructive procedures, including evisceration, enucleation, and exenteration. The purpose of this study was to analyze, over a five year period, the number of eye destructive procedures and investigate the most common indication for said procedures. Methods: After obtaining IRB approval, all medical records from August of 2010 February of 2015 from patients having eye destructive procedures performed by one surgeon at one academic tertiary care facility were reviewed, investigating clinical indication for the procedure. Results: There were 103 eye destructive procedures performed on 101 patients at one institution over the roughly 5 year period. Of these 103, 69% of the procedures were enucleations, 27% were exenterations and 4% were eviscerations. The two most common indications for procedure were trauma (40%) and malignancy (34%). The other noted indications were blind painful eye (15%), infection (10%) and ruptured cornea (1%). Discussion: As one might imagine, more complicated cases were very common indications for eye destructive procedures at a tertiary care center. The hospital is a level I trauma center, which would account for a high volume of trauma cases. Also, given that there is a large cancer center, the high incidence of malignancy is accounted for as well. There were also five exenterations performed because of invasive mucormycosis. In these five patients, four had known malignancies and one had immunodeficiency, secondary to unknown reason, which was being worked up at the patient s time of death. These numbers suggest that often complicated orbital trauma and malignancies are transferred or referred to tertiary care centers for definitive management and treatment. Our institution has a large cancer center, which contributes to our significant number of procedures secondary to those malignancy, as well as malignancy related infections. References: 1. Hansen, Anja Bech, et al. "Review of 1028 bulbar eviscerations and enucleations, Changes in aetiology and frequency over a 20 year period." Acta Ophthalmologica Scandinavica 77.3 (1999): 331 335. 2. Rasmussen, Marie Louise Roed, et al. "Review of 345 eye amputations carried out in the period 1996 2003, at Rigshospitalet, Denmark." Acta ophthalmologica 88.2 (2010): 218 221. 3. Zheng, Chengjie, and Albert Y. Wu. "Enucleation versus evisceration in ocular trauma: a retrospective review and study of current literature." Orbit 32.6 (2013): 356 361. 4. Vemuganti, Geeta K., et al. "Enucleation in a tertiary eye care centre in India: prevalence, current indications and clinico pathological correlation." Eye 15.6 (2001): 760 765.

Virtual Reality Technology and Vision by Abiodun E. Akinwuntan, PhD, MPH, MBA Dean 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 Assessments for driving Typical Visual acuity and Perimetry (state driving laws) 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 Driving related Perception (color & depth) Sensitivity (contrast & glare) Useful Field of View (UFOV) Cognitive (memory, search, spatial) Driving (simulator and on road)

First study The Useful Field of View apparatus Dynavision apparatus 7 Patients with age related macular degeneration Investigate the effect of training on driving performance plus Rehabilitation consisted of 10 hours of static versus dynamic vision training Driving Simulator Result Lane positioning Brake reaction time Overtaking Road sign recognition Hazard perception Anticipation Akinwuntan et al, Arch Phys Med Rehabil, 2014 Visual exploration and cognitive workload during a visual search task in individuals with PD Objectives cognitive workload = degree of mental effort needed to execute a task 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 electroencephalogram Pupillometry Maud Ranchet, John Morgan, Abiodun E. Akinwuntan, Hannes Devos

Methods Visual search task 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) Pre identified target ABSENT PRESENT 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 FOVIO Eye tracker Left eye Right eye 42 trials 21 trials with target present 15 s per trial Results 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 0.049 Number of errors 4.6 3.2 3.4 4.1 5.3 2.7 0.21 Number of omissions 0.9 1.5 1.5 1.9 5.6 6.1 0.12 Correct Response times 7.3 1.4 8.1 1.4 9.4 1.7 0.01 Outcomes: Correct responses; Errors; Omissions; Correct response times Fixation duration; Cognitive workload (0 1) Correct responses (max score = 44), n 40 30 20 10 0 * Controls Patients - NCI * Patients - MCI Response times (s) 12 10 8 6 4 2 0 ** 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%) Discussion Larger sample sizes 1 0.8 controls 0.6 0.4 0.2 0 0% 20% 40% 60% 80% 100% Moment of stimulus onset % of response times moment of response = press the present button 9 controls, 5 patients-nci, 7 patients-mci cognitive workload CONTROLS PATIENTS WITH NO APPARENT COGNITIVE IMPAIRMENT The cognitive workload good marker of early cognitive decline in individuals with Parkinson s disease with no cognitive impairment apparent

Methods Driving simulator desktop Performance-Based Visual Field Testing in Drivers with Glaucoma 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 19 20 First scenario: C1 Aim: To investigate the effect of visual field performance Task: Focus on the white square and press the button as soon as a red square appears 21 22 Second scenario: C2 Aim: To investigate the effect of dynamic condition (visual flow) Task: White central fixation point has been replaced by lead vehicle Automatic pilot at 45 mph Focus on the lead vehicle and press the button for each red symbol 23 24

Third scenario: C3 Aim: To investigate the effect of driving activity on the visual field performance Task: The participant has follow a lead vehicle driving 45 mph Speed warnings if the driver is above 50 or below 40 mph Random wind gusts to keep driver attentive Press the button for each red target symbol 25 26 Fourth scenario: C4 Aim: To investigate the effect of driving context on the visual field performance Task: Drive while obeying all traffic rules Press 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 Visual Field (VF) and Driving 36 states in the US have binocular horizontal VF requirements (15 = 140 0 ; 18 = 105 0 130 0 ; 1 = 150 0 ) Kansas and Arkansas further specified the horizontal VF requirement for drivers with only one useful eye (55 0 105 0 ) 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 29 In 2 states, no driver s license for a person with homonymous hemianopia 30

Visual Field (VF) and Driving Visual Field (VF) and Driving Healthy drivers 10 visual field deficits Interpupillary distance and facial anatomy 31 32 Thank you and questions

Gerhard W. Cibis MD Clinical Prof. Ophth. KU Eye Emeritus Chief CMH Microtropia (Lang) Mono fixation (Parks) Prevalence,Significance Evolution,Diagnosis with the Brueckner red reflex test 40% of treated esotopes (surgery or glasses) end up microtropic Traditional tests for microtropia are impossible in children Bruckner red reflex helps identify microtropes Pupil Red Reflex "Brueckner Test" Indicates Fixation Strabismus Refractive Error Superior Crescent from Hyperopia Aligned by Hirschberg Hyperopic Superior Crescent Disappears with glasses correction

Inferior Myopic Crescent OU OD Hyperopic crescent +5 Cherry Red OS +1.5 minimal crescent Orthotropic 3/3 Lang Stereo Not Accommodating Aligned Alternating Mic ET OD Mic ET OS Mic ET OD ET Accommodating

Not Accommodating no Crossing Residual R Mic with 18 BO prism no diplopia OD ET OS Fixing 17year old modest myope acute onset diplopia alternating esotropia Still Microtropic with 18 BO Prism L Mic ET 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 scotoma L 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 eye allows for peripheral fusion without diplopia Suppression scotoma in the deviated eye allows for the following characteristics Fusion of Worth 4 dot lights at near where they fall outside of the suppression scotoma but not at distance where a light falls within the scotoma Steroacuity between 3000-60 seconds arc on Titmus but zero on Lang or other Random Dot Stereograms 4 diopter base out prism displaces the image within 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 to refixate the target but the microtropic eye fails to reconvert These observations are very hard in practice impossible 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 Am Ophthalmic 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.

Common Cataract Surgery Difficulties: How to Avoid or Manage Them (video presentation) Luther Fry, MD Volunteer Faculty, KU Eye Effect of ocular hypotensive drops given immediately after cataract surgery on 3 and 24 hour post op IOP. Summary of our multiple studies; 8 studies, approximately 1000 patients, scattered over the past 3 years. Cosopt BEST, Combigan, Simbrinza and Timolol 0.5% next, Trusopt and Alphagan next. Pilocarpine 2%, Betoptic S and Lumigan NO BETTER than control (artificial tears). Systemic carbonic anhydrase inhibitors NO BETTER than topical. Generics as good as brand name. So, we now use: generic Cosopt for non asthmatics; Simbrinza for asthmatics and NO systemic CAIs. 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 Al Lemoine Medical School= Dr. Lemoine Residency= Chief Volunteer Faculty= Al Family Man Clinician Educator Leader Clinician Premier cataract surgeon Excellent diagnostician Educator Medical students and residents Massachusetts Eye and Ear Infirmary Lancaster Course

Leadership Notable Faculty KU Chairman Recruited volunteer faculty, his practice included 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 Bob Sinskey Steve Shearing Tom Mazzocco Manus Kraff Dick Kratz

Cataract Surgical Technique Intracapsular Cataract Extraction Planned Extrcapsular Cataract Extraction Phacoemulsification Incision= stainless steel blade Paracentesis tapered Two step primary incision (2.7 mm internally) Visco elastic Femto Laser Assisted Cataract Surgery 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 Intracapsular Cataract Extraction Intolerable unwanted optical image Conclusion Thanks for your attention Thanks for the honor to remember Dr. Lemoine

3/24/2016 Femtosecond laser assisted cataract extraction of posterior polar cataracts 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 Chetan Soni, MD, FACS. Viscoelastic cohesive Capsularrhexis optimum size between 4 5 mm. Large capsularrhexis may not support sulcus fixated IOL, small may lead to difficulty in prolapsing nucleus if need be. 1 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 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. 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. 1

3/24/2016 Femtodelineation Technique first described by Dr. A. R. Vasavda (ref) Surgical videos Outcome of our 11 case series Thank you. 2

Refractive Lens Exchange None Financial Disclosure Jason Stahl, MD Durrie Vision Overland Park, KS Refractive Lens Exchange Baby Boomers 4 in 1 procedure Distance Vision Near Vision Eliminates future cataract surgery Stable Vision 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 Dysfunctional Lens Syndrome 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 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 Stage 1 DLS: HD Analyzer Results Mid-normal OSI, MTF, and PSF. Good predicted VA 23 year old lens 48 year old lens 55 year old lens Stage 1 DLS Stage 2 DLS 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 Stage 2 DLS Moderately increased back scatter Increasing yellow discoloration

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 Stage 3 DLS: HD Analyzer Results Poor PSF Poor MTF Poor predicted VA Moderate to poor OSI Recommend refractive cataract Stage 3 DLS Stage 3 DLS: Densitometry Greatly increased nuclear density Stage 3 DLS: Slit Lamp Exam Stage 3 OD and Stage 2 OS Greatly increased back scatter. Yellow to brunescent discoloration Cloudy appearance

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 Defocus Curve - Binocular Intermediate Intermediate Distance P<0.05 Distance Near Near My (Simple) Approach: Quality > Range My (Simple) Approach: Quality > Range Dominant Eye Tecnis One/Toric Target distance Best image quality and quantity Non-Dominant Eye (2 options) 1. Blended Vision Tecnis One/Toric Target: -1.00 to -1.50 D (based on pupil size) 80-90% spectacle free Occasional +1.00 D OTC readers and/or night driving glasses Candidates Previous corneal refractive surgery Corneal aberrations Small pupils Increase depth of focus Concerned about visual quality

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 CE Marked IC-8 IOL Design (Acufocus) 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 20/50 20/40 20/30 20/20 20/10 20/50 20/40 20/30 20/20 20/10 20/50 20/40 20/30 20/20 20/10 Depth of Focus Comparison Optical Modeling, 3.0 mm Pupil IC-8 Small Aperture IOL Extended Depth of Focus (TC -0.75D) 0.0 D -0.5 D -1.0 D -1.5 D -2.0 D -2.5 D Standard Mono-focal 0.0 D -0.5 D -1.0 D -1.5 D -2.0 D -2.5 D 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) 46 IC-8 IOL Extends Depth of Focus 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 Acuity (LogMAR) -0.20-0.10 0.00 0.10 0.20 0.30 0.40 0.50 0.60 0.70 0.80 0.90 1.00 1.10 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 Cylinder Defocus Curves IC-8 vs Monofocal Change in Visual Acuity (logmar) 0 0.05 0.1 0.15 0.2 0.25 One line of loss IC-8 Monofocal Defocus Lens Power Simulated Monofocal IOL Ang 6M (n=8) 0.3 0-0.5-1 -1.5-2 -2.5-3 N=10 Cylinder Defocus Data courtesy of Robert Ang, MD

CE Mark AMO Symfony Currently in FDA Clinical trials Tecnis Monofocal AMO Symfony 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 lensbased 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 advanced severe uveitis Selection is key Younger tend to be better Macular edema still challenging If possible, get it inactive Case 1 HPI 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 Disease Hassan Al Dibhi et al Sept 2011 Pars plana vitrectomy with internal limiting membrane removal for a macular hole associated with Behçet's disease T T Wu and M C Hong 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 nonoperated eyes EXCEPT for 1 patient who did not have macular ischemia

Back to our patient Patient underwent PPV/membrane peel/c3f8 13% gas 6.12.15 OCT POM#1 and #2 Question? Now her vision is 20/100 OD 20/80 OCT at POM#1 How would you manage this patient now? Observe vs re-operate? She underwent second PPV/membrane peel/c3f8 13% gas 10.21.15 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 J Ophthalmol 1995;119:752 9. Spaide RF: Measurement of the posterior precortical vitreous pocket in fellow eyes with posterior vitreous detachment and macular holes. Retina. 23:481 485 2003 Privat E, Tadayoni R, Gaucher D, et al.: Residual defect in the foveal photoreceptor layer detected by optical coherence tomography in eyes with spontaneously closed macular holes. Am J Ophthalmol. 143:814 819 2007 Criteria for diagnosis of Behçet sdisease. 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 uncommon complication 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.

Risk Factors for Intraocular Pressure Elevation After Dexamethasone Intravitreal Implant Julie Quick, MD, Resident Class of 2017 Primary Supervisor: Paul Munden, MD Purpose: Intravitreal steroids are a recognized cause of increased intraocular pressure (IOP). The goal of this study was to analyze what risk factors are associated with the dexamethasone intravitreal implant 0.7 mg (DEX implant) and what medical and surgical interventions were necessary to control the IOP. Methods: A retrospective, descriptive, chart review was performed after IRB approval. All patients who received a DEX implant by a single retinal surgeon in our department between 2014 and 2016 were identified. In each case, gender and age of the patients, diagnosis, number of reinterventions and laterality were registered. Results: Out of 48 patients (60 eyes) who received the DEX implant, 13 eyes (22%) had an IOP elevation > 5mmHg from baseline. On average, peak IOP was 6 weeks after injection. Eight eyes (62%) with IOP elevation were adequately controlled with an average of two IOP lowering drops; 4 eyes (30%) required filtering surgery and 1 eye (8%) did not require intervention, as the IOP was < 21mmHg. The most common diagnosis associated with elevated IOP was posterior uveitis (30%) followed by DME (27%), BRVO (18.8%) and CRVO (12.5%). Nine patients had a history of primary open angle glaucoma (POAG). Of these patients, 3 had an IOP elevation > 5mmHg. Two of these patients were not taking IOP lowering medications at the time of their injection. The 6 patients who did not have an IOP elevation were already on either an IOP lowering drop or had a history of glaucoma surgery. All 4 patients with a known history of increased IOP after topical steroids had an IOP elevation after DEX implant. Conclusions: The majority of patients who had an elevated IOP after DEX implant were controlled with IOP lowering medications. A history of glaucoma that is untreated, posterior uveitis, DME, and history of steroid response are potential risk factors for IOP elevation and should be monitored closely.

Pattern Dystrophy: Case Series Luke Dolezal, MD, Resident, Class of 2018 Primary Supervisor: Ajay Singh, MD Pattern dystrophies are a group of macular diseases characterized by various patterns of pigment deposition and lipofuscin accumulation within the macula due to RPE dysfunction. Patterns may fluctuate in individual patients over time and may differ between eyes. Disease onset is typically in the 5 th 6 th decade. They have a relatively good visual prognosis, although slow progressive central vision loss may occur, including severe vision loss in up to 50% of patients after age 70, due to chorioretinal atrophy and/or CNV. Patients diagnosed at an older age may be misdiagnosed as having age related macular degeneration, due to a similar fundus appearance. Accurate diagnosis is important to avoid unnecessary treatment and patient anxiety. This presentation will review cases of Pattern Dystrophy seen at KU Eye Clinic. We will discuss clinical features and multimodal imaging used in the diagnosis and monitoring of these patients.

Clinical features of diabetic retinopathy A Neural Perspective on Diabetic Retinopathy Rithwick Rajagopal, M.D., Ph.D. Assistant Professor Department of Ophthalmology and Visual Sciences Washington University School of Medicine Mild to severe Progressive (requires passage through intermediate stages) Exclusively vascular features Early events in diabetic retinopathy Histologic and electron micrographic findings April 9, 2016 No financial disclosures A Current View of DR Progression DM Elevated glucose Microvascular Damage; Inflammation; Loss of Endothelial Integrity Microaneurysms Hemorrhages Macular Edema Ischemia Proliferation VEGF 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 Other assays of visual function Multi-focal ERG Measures of contrast sensitivity Perimetry Prospective clinical trials An Alternative Model for DR Progression Development of a relevant animal model DM Dysregulated insulin signaling; Elevated glucose Neuroretinal Damage Neuroinflammation; Visible Microvascular Defects 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 Loss of Neurovascular Coupling Classic Retinopathy

Detection of retinopathy in rodents Rodent electroretinography Trypsin-digest analysis of retinal microvasculature Capillary leakage assays Detection of retinal inflammatory mediators 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! 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 2. Disease occurs in stages, and inner retinal dysfunction occurs early 3. This pattern is consistent with human disease

Acknowledgements Clay Semenkovich, MD Sheng Zhang Li Yin Xiaochao Wei, PhD Larry Spears, PhD Peter Lukasiewicz, PhD Greg Bligard WUSTL DOVS Core Labs Anne Hennig, PhD Belinda Dana Guanyi Ling Funding Horncrest Foundation K08-EY-025269 P30-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 plexus 11,12 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. Mar 1980;87(3);229-233. 7. Rosenberg ME, Tervo TM, Immonen IJ, Muller LJ, Gronhagen-Riska C, Vesaluoma MH. Corneal structure and sensitivity in type I diabetes mellitus. Investigative Ophthalmology & Visual Science. Sep 2000;41(10):2915-2921. 8. Parra A, Madrid R, Echevarria D, et al. Ocular surface wetness is regulated by TRPM8-dependent cold thermoreceptors 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 selective stimulation 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 diabetic retinopathy: an in vivo confocal study. Investigative Ophthalmology & Visual Science. Nov 2009;50(11):5155-5158. 12. Misra S, Ahn HN, Craig JP, Pradhan M, Patel DV, McGhee CN. Effect of panretinal photocoagulation on corneal sensation and the corneal subbasal nerve plexus in diabetes mellitus. Investigative Ophthalmology & 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 with proliferative 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 microvascular complications in people with type 2 diabetes mellitus. Journal of diabetes and its complications. Sep-Oct 2013;27(5):459-462. 17. Methodologies to diagnose and monitor dry eye disease: report of the Diagnostic Methodology Subcommittee 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 eye disease. American Journal of Ophthalmology. May 2011;151(5):792-798 e791.

UPDATE ON DIABETIC RETINOPATHY AND DME MANAGEMENT GLUCOSE ALDOSE REDUCTASE NADPH NADP SORBITOL OSMOTIC DAMAGE Lens changes Kansas Eye Con 2016 APOPTOSIS April 8 & 9, 2016 Natalia Villate, M.D. HYPERGLYCEMIA PERICYTE DAMAGE AGE RAGE ENDOTHELIAL CELL DYSFUNCTION INFLAMMATION DIABETIC RETINOPATHY NEURO DEGENERATION 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. Dr Villate is co-investigator in all current trials at FLEI. Genentech and Regeneron provided original slides of clinical trial results used in this presentation 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 loss 2-5 In the eye, overexpression of VEGF is associated with DME, wamd, and macular edema following RVO 1-3 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. 11 MAYOR CHANGES IN LAST DECADE 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. DIABETES PREVALENCE IN THE US In 2010, 25.6 million people 20 years old in the US had diabetes 1 11.3% of the population 1 By 2020, prevalence is expected to rise to 15% of adults in the US (39 million) 2 2009 Estimates of the Percentage of Adults 20 Years Old With Diagnosed Diabetes 3 Age-adjusted percent 0-6.3 6.4-7.5 7.6-8.8 1. Centers for Disease Control and Prevention Website. National Diabetes Fact Sheet, 2011. 8.9-10.5 http://www.cdc.gov/diabetes/pubs/factsheet11.htm. Accessed May 18, 2012. > 10.6 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.

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. MICRO- AND MACROVASCULAR COMORBIDITIES IN PATIENTS WITH DIABETES 1-5 Patients can reduce the risk and severity of DME by controlling their ABCs 6,7 : A 1c Blood pressure Cholesterol 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% Stroke in patients 35 years of age or older 21.9% Coronary heart disease* in patients 35 years of age or older 29.9% Diabetic nephropathy in diabetes patients 60% to 70% Diabetic neuropathy in 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. 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 MAJORITY REMAIN UNDIAGNOSED OR UNTREATED American Academy of Ophthalmology: Recommended Eye Examination Schedule (Including Dilated Eye Exam) for Diabetic Patients Diabetes Type Recommended Time for First Examination Recommended Follow-up Type 1 3 5 years after diagnosis Yearly Type 2 At time of diagnosis Yearly 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 SO WHAT IS NEW 40% 50% of diabetic patients do not receive recommended eye care 1 Joslin study of patient self-awareness of DR 2 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 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. ETDRS Overall, decreased moderate visual loss by ~ 50% Add anti VEGF to laser or possibly replace laser. Treated group 13% Control group 22% Moderate visual loss Use Steroids to treat inflammatory component of retinopathy Medical management matters more than many of us realize. ETDRS Report #1 Arch Ophthalmol 103:1796-806, 1985

RIDE/RISE MACULAR AND PANRETINAL LASER TREATMENT THROUGH MONTH 24 HOW DOES ANTI VEGF MEDICATIONS AFFECT DIABETIC RETINOPATHY? Outcome Measure Pooled RIDE and RISE Sham LUCENTIS (n=257) 0.3 mg (n=250) Received macular laser a 72.0% 37.6% Mean no. of treatments b 1.7 0.7 Received panretinal laser 11.7% 0.8% a Exploratory 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]). b P<0.0001 for all LUCENTIS groups vs sham (Wilcoxon test [stratified]). Beginning at month 3, patients were evaluated monthly for 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 prior 3 months, and evaluating physician deems laser therapy to be beneficial. LUCENTIS FDA Briefing Book. Month 24 Month 36 a Pooled RIDE and RISE enrollment. Nguyen et al. Ophthalmology. 2012;119:789. RIDE AND RISE - STUDY DESIGN Objective: Evaluate efficacy and safety of intravitreal RANIBIZUMAB compared with sham injections in patients with center-involved DME Screening: BCVA 20/40 to 20/320, OCT CST 275 μm Sham Injection (n=257) a DME 1:1:1 Randomization (one eye per subject) RANIBIZUMAB 0.3 mg (n=250) a,b RANIBIZUMAB 0.5 mg (n=252) a 24-Month Controlled Treatment Period (monthly intravitreal/sham injections; macular laser, if eligible, beginning month 3) Monthly RANIBIZUMAB 0.5 mg Monthly RANIBIZUMAB 0.3 mg b Monthly RANIBIZUMAB 0.5 mg Long-term Open-label Extension With 0.5 mg LUCENTIS RANIBIZUMAB is approved for a 0.3-mg dose in DME Primary Endpoint RIDE/RISE KEY FINDINGS 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 RIDE/RISE 15 ETDRS LETTERS FROM BASELINE AT MONTH 24 (PRIMARY ENDPOINT) RIDE/RISE VIVID and VISTA:Study Design Pooled RIDE and RISE 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) Percent of subjects = 24.0 (P<0.0001) a Percentages of patients who lost 15 letters from baseline at month 24 (secondary endpoint) LUCENTIS 0.3 mg: 2.0% Sham: 9.3% IVT Aflibercept 2 mg q4 wks Patients randomized 1:1:1 IVT Aflibercept 2 mg q8 wks* Laser Photocoagulation Sham (n=257) 0.3 mg (n=250) Primary endpoint: Mean change in BCVA Primary Endpoint: Week 52 Key Secondary endpoints Change in OCT Change in Diabetic Retinopathy Severity Scale (DRSS) a Cochran-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 HbA 1c ( 8%, >8%), and prior treatment for DME (yes, no). LUCENTIS FDA Briefing Book. *After 5 initial monthly doses Continued treatment through Year 3

Proportion of Patients Gaining 10 and 15 Letters at Week 100 PRIMARY ENDPOINT KEY FINDINGS Proportion of patients VIVID VISTA 100% 80% 63.6% 58.1% 59.6% 60% 49.6% 38.2% 38.3% 40% 31.1% 33.1% 27.9% 25.0% 20% 12.1% 13.0% 0% 15 letters 15 letters 10 letters 10 letters 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. Laser IAI 2q4 IAI 2q8 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) 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 µm 0-50 -100-150 -200-250 0-50 -100-150 Mean Change in Central Retinal Thickness Through Week 100 SECONDARY ENDPOINT Week 0 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 VIVID VISTA - 195* - 192* -200-186* -250-183* 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. -66-73 -86 Laser -196 IAI 2q8-212 IAI 2q4 *P<0.0001 vs laser -84 Laser -191* IAI 2q4-191* IAI 2q8 DRCR NETWORK COMPLETED PROTOCOLS 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* 66023 100% Proportion of Patients With 2 Step Improvement in DRSS at Week 100 SECONDARY ENDPOINT VIVID VISTA DRCR NETWORK ONGOING PROTOCOLS Proportion of patients 80% 60% 40% 20% 8.2% 29.3% 32.6% 15.6% 37.0% 37.1% Laser IAI 2q4 IAI 2q8 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 0% 85 82 86 154 154 151 DRCR Network Participant Total Since 2003 8807 P=0.0004 2q4 vs laser P<0.0001 2q8 vs laser P<0.0001 2q4 vs laser P<0.0001 2q8 vs laser * Enrollment done/in active follow-up; **Recruiting 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 forward DRSS, Diabetic Retinopathy Severity Score

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 MEAN CHANGE IN VISUAL ACUITY AT FOLLOW-UP VISITS AMONG EYES THAT WERE PSEUDOPHAKIC AT BASELINE* Visit Week * Values that were ±30 letters were assigned a value of 30 28 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 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 29 *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 CHANGE IN VA OVER 5 YEARS STRATIFIED BY BASELINE VA Test for interaction at 5 Year time point: P = 0.001 Test for interaction from longitudinal model: P = 0.004 27 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 baseline 30

RESTORE WHAT ABOUT RANIBIZUMAB ALONE? RBZ RBZ + Laser 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. Laser alone --The Restore Study: Ranibizumab monotherapy or combined with laser versus laser monotherapy for diabetic macular Edema Ophthalmology 2011;118:615 25. READ 2 THREE YEAR OUTCOMES Mean number of injections 2.3 p=0.08 5.4 +2.0 letters 24 μm -1.6 letters -36μm HOW ABOUT AVASTIN? PACORES and BOLT 3.3 p=.11 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. PACORES 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. 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 Results Arevalo et al. Br J Ophthalmol 2016.

BOLT DME TREATMENT: ANTI-VEGF (COMPLETERS OF THE GIVEN VISIT ONLY) 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). Aflibercept Bevacizumab Ranibizumab Global P-Value # of Injections: Median (25 th, 75 th 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 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. 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. 40 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) HOW DO ANTI VEGF AGENTS COMPARE? At least one focal/grid laser Aflibercept Bevacizumab Ranibizumab Year 1 37% 56% 46% Global P- Value <0.001 * Year 2 20% 31% 27% 0.046 Over 2 Years 41% 64% 52% <0.001 41 *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. DIABETIC RETINOPATHY CLINICAL RESEARCH NETWORK SUBGROUP ANALYSIS 1 YEAR RESULS Aflibercept, Bevacizumab, or Ranibizumab for DME: Two-year Results PROTOCOL 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 Mean Change is Visual Acuity Letter Score 20 15 10 5 0 20/32-20/40 0 8 16 24 32 40 48 Visit Week ~+8 20/50 or worse 0 8 16 24 32 40 48 Visit Week +19 +14 +12 Aflibercept Bevacizumab Ranibizumab

15 LETTER IMPROVEMENT AT 2 YEARS 20/32 20/40 20/50 or wose Observed Data Observed Data WHAT ABOUT PRP? Percent *P 0.89 20% 17% 19% Percent 58% *P 0.75 52% 55% PROTOCOL S Prompt PRP vs. Ranibizumab + Deferred PRP for PDR Study * P-values adjusted for baseline visual acuity and multiple comparisons POST HOC ANALYSIS OF APTC ADVERSE EVENTS STRATIFIED BY PRIOR MI/STROKE % 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. 44 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 KEY FINDINGS PROTOCOL T 2 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 MEAN CHANGE IN VISUAL ACUITY AREA UNDER THE CURVE ANALYSIS Mean Visual Acuity Change (Letter Score) 15 10 5 0-5 Adjusted Mean Difference over 2 years (AUC): +4.2 P-value<0.001 95% Confidence Interval: (+3.0, +5.4) + 4.5-0.3 0 16 32 52 68 84 104 N = 191 N = 160 Visit Week N = 203 N = 168 Ranibizumab Group PRP Group 48 Area under the curve (AUC) analysis: Pre-planned secondary outcome

49 Mean Visual Acuity Change (Letter Score) 14 12 10 8 6 4 2 0-2 -4 Mean Change in Visual Acuity Stratified by Baseline DME With Baseline DME +7.9 +2 Without Baseline DME +1.8-0.5 0 16 32 52 68 84 104 0 16 32 52 68 84 104 N = 42 Visit Week N = 33 N = 147 Visit Week N = 126 N = 46 N = 37 N = 155 N = 130 Ranibizumab Group PRP Group *Outlying values were truncated to 3 SD from the mean KEY FINDINGS PROTOCOL S PRP remains effective for PDR in 21 st 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 52 through 5 years PERIPHERAL VISUAL FIELD OUTCOMES 2-YEAR VISIT Ranibizumab Group (N = 58) Cumulative Point Score Change from Baseline Humphrey Visual Field 30-2 + 60-4 PRP Group (N = 57) Mean -23-422 WHAT ABOUT STEROIDS? 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) 50 PROPORTION OF EYES DEVELOPING CENTER INVOLVED DME WITH VISION IMPAIRMENT (EYES WITHOUT BASELINE DME AND VISION IMPAIRMENT) 2-Year Adjusted Difference: 19% 95% Confidence Interval: (10% to 28%) P-value < 0.001 N = 155 N = 147 51 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

STEROIDS FOR DME: CLINICAL TRIALS 66 yo, phakic. NIDDM diagnosed in May 2014. Metformin/Glipizide/Lisinopril Initial eye exam Severe NPDR with DME A1C 9% 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. 10/24/2014 OD 20/100 s/p Avastin x 3 560µ 10/24/2014 OS 20/100 s/p Avastin x 3 637µ 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. 67 yo, phakic. 1 year later (11/04/2015) A1C 6.9% OD: 20/60 (3 line gain) 163 µ decrease CFT s/p 11 Injections (6L 5 E) s/p 1 Focal laser OS: 20/60 (3 line gain) 170 µ decrease CFT s/p 12 Injections (7L 5 E) s/p 1 Focal laser 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 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 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

FIBRATES AND STATINS: FIELD STUDY BUT, THERE MAY BE INCREASED COSTS Economic considerations of macular edema therapies. Smiddy WE.Ophthalmology. 2011 Sep;118:1827-33. 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. FIELD (OPHTHALMOLOGY SUB STUDY) ETDRS photos performed on 1012 subjects Lancet 2005; 366: 1849 61 Lancet, 2007: 370, 1687-1697. DO NOT FORGET LASER 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. 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 course of response to focal/grid photocoagulation for diabetic macular edema. Diabetic Retinopathy Clinical Research Network. Retina. 2009;29:1436-43. 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 WHAT ABOUT SYSTEMIC DIABETES CONTROL? 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 Education During Retinal Ophthalmology Visits on Diabetes Control (Protocol M) Thank You

Worldwide Rates of Diabetic Retinopathy The microvascular pathology of diabetic retinopathy Rithwick Rajagopal, M.D., Ph.D. Assistant Professor Department of Ophthalmology and Visual Sciences Washington University School of Medicine 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 April 9, 2016 No financial disclosures Current treatments for microvascular disease due to diabetes The Transformative Effect of VEGF Antagonism 1. Glucose control (with glycated hemoglobin being the endpoint). 2. VEGF antagonism 3. Laser 1. Review of relevant clinical trials 2. Comparative efficacy 3. Safety concerns 4. Corticosteroids The role of VEGF in maintenance of healthy retina The Glucose-Centric Diabetic Retinopathy Hypothesis 1. Overview of expression of VEGF and its receptors in the retina 2. Concerns for chronic antagonism DM Elevated glucose Microvascular Damage; Inflammation; Loss of Endothelial Integrity Microaneurysms Hemorrhages Macular Edema Ischemia 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 What Molecules are Altered in the Retina with Fenofibrate Therapy? 1. Screening for candidates 2. Validation of putative targets 3. Modification of retinal lipid environment 4. Anti-inflammatory actions

Acknowledgements Clay Semenkovich, MD Sheng Zhang Li Yin Xiaochao Wei, PhD Larry Spears, PhD Washington University Retina Service P. Kumar Rao, MD Rajendra Apte, MD, PhD Stanford Taylor, MD DOVS Core Labs Anne Hennig, PhD Belinda Dana Guanyi Ling Funding Horncrest Foundation K08-EY-025269 P30-EY-002687 Research to Prevent Blindness Contact: rajagopalr@vision.wustl.edu // Referrals: 314-362-EYES

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 Diagnosis Set IOP Goal Initiate and Optimize Therapy Monitor IOP Disc Photos ON OCT Automated VF Stable Progression Confirm Progression Add or Alter Therapy Reset GPA Baseline Fields 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

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 GPA Reports 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 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 Clinical Interpretation 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. 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

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 KU MD and Residency Alumni 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

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 KU MD and Residency Alumni 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

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 KU MD and Residency Alumni 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

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 KU MD and Residency Alumni 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

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 KU MD and Residency Alumni 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

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 KU MD and Residency Alumni 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 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 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

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