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Kansas Kansas EyeCon EyeCon

May 8 & 9, 2015 KU Edwards Campus BEST Conference Center 12604 Quivira Overland Park, KS 66213

Sponsored by the University of Kansas Department of Ophthalmology and the Lemoine Alumni Society

Kansas EyeCon 2015

We wish to acknowledge and sincerely thank these organizations for exhibiting at this conference: Platinum Sponsors:

Alcon Laboratories, Inc. Bausch + Lomb Ellex Glaukos Corporation Katena Instruments & Biologics Regeneron Pharmaceuticals, Inc. Silver Sponsors: Sightpath Medical

Allergan, Inc. Bruce Biscanin Carl Zeiss Meditec, Inc. Heidelberg Engineering Quantel Medical NanoPac, Inc. Bronze Sponsor:

KU Audio‐Reader Network Kansas EyeCon 2015 KU Edwards Campus, BEST Conference Center Overland Park, KS May 8 & 9, 2015

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:

Neuro-Ophthalmology & Pediatrics Session 1. Identify changes in the diagnostic criteria for intracranial hypertension and apply recommended changes in treatment protocols for intracranial hypertension; 2. Review pediatric uveitis etiologies and common pediatric uveitis treatments; 3. Describe the standard systemic work-up for new-onset pediatric uveitis; 4. Review steroid-sparing agents for the treatment of pediatric uveitis.

Anterior Segment & Orbito-Plastics Session 5. Describe the pathophysiology and mechanisms of intraocular pressure elevation in neovascular glaucoma; 6. Discuss the rationale for therapeutic approaches to neovascular glaucoma including the use of anti-VEGF agents; 7. Evaluate outcomes of trabeculectomy bleb needle revision with 5-fluorouracil; 8. Investigate relationship between outcomes and mechanism of glaucoma; 9. Outline the experimental model of pressure modulation in Baerveldt implants; 10. Discuss the clinical application of tubing inserts in Baerveldt implants for the reduction of post-operative hypotony; 11. Describe the presentation and differential diagnosis for osseous tumors commonly presenting with orbital involvement; 12. Discuss the medical and surgical management of osseous orbital tumors, including review of current literature; 13. Review orbital anatomy, orbital disease, and medical and surgical options; 14. Demonstrate a few simple maneuvers which may be helpful in avoiding/managing problems in routine cataract surgery, including surgicenter tips that may be helpful in efficiency and patient satisfaction.

Retina Session 15. Review current recommendations for genetic testing for diagnostic of affected individuals and family members at risk to have affected offspring; 16. Review reported results and ongoing trials using gene therapy for inherited retinal disorders; 17. Evaluate the evidence regarding treatment of center involving macular edema with laser, VEGF inhibitors and steroids; 18. Evaluate the evidence for treatment of diabetic macular edema at the time of cataract surgery; 19. Correctly make a diagnosis when patients present with sub retinal fluid (SRF) in the elderly age group and management of these cases once a diagnosis is made; 20. Summarize photomechanical, photothermal and photochemical retinal injuries; 21. Analyze countermeasures against clinical and industrial photic injuries; 22. Determine if micropulse laser is effective in reducing macular edema and identify any relationships that promote better or worse outcomes; 23. Examine the effectiveness of dexamethasone intravitreal implant as adjunctive or sole treatment of persistent uveitis macular edema patients with Multiple Sclerosis.

Cornea Session 24. Review historical techniques important to the development of current pterygium surgery; 25. Recognize newer techniques and materials used for pterygium surgery; 26. Describe the importance of properly done corneal cultures to help guide treatment in keratitis; 27. Discuss the relationship between diabetes mellitus and ocular surface disease, and diabetes mellitus and tear osmolarity; 28. Identify the mechanism of action by which Omega-3 free fatty acids will treat Dry Eye Disease; 29. Identify the principle endpoints of the clinical trial DREAM (Dry Eye Assessment and Management Study).

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

CME Credit Provided by AKH Inc., Advancing Knowledge in Healthcare Physicians This activity has been planned and implemented in accordance with the Essential Areas and policies of the Accreditation Council for Continuing Medical Education (ACCME) through the joint providership of AKH Inc., Advancing Knowledge in Healthcare and the University of Kansas, Department of Ophthalmology and The Lemoine Alumni Society. AKH Inc., Advancing Knowledge in Healthcare is accredited by the ACCME to provide continuing medical education for physicians. AKH Inc., Advancing Knowledge in Healthcare designates this live activity for a maximum of 6.5 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 Anna Berry, MD, MPH N/A Nothing to Disclose Miranda Bishara, MD N/A Nothing to Disclose Michelle Boyce, MD N/A Nothing to Disclose Emily Broxterman, MD N/A Nothing to Disclose Mary Champion, MD N/A Nothing to Disclose Alina V. Dumitrescu, MD N/A Nothing to Disclose Luther L. Fry, MD N/A Nothing to Disclose Derek Horkey, MD N/A Nothing to Disclose Martin A. Mainster, PhD, MD, FRCOphth. 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 Matthew Recko, MD N/A Nothing to Disclose Ajay Singh, MD N/A Nothing to Disclose Jason Sokol, MD N/A Nothing to Disclose John Sutphin, MD N/A Nothing to Disclose R.C. Andrew Symons, MD, PhD N/A Nothing to Disclose W. Abraham White, MD N/A Nothing to Disclose Thomas J. Whittaker, MS, JD, 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. DISTINGUISHED LEMOINE 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 Alumni Speakers

Luther L. Fry, MD MD: 1967

Thomas Whittaker, JD, MD, MS MD: 1990 AGENDA Kansas EyeCon May 8 – 9, 2015

KU Edwards Campus Friday, May 8, 2015 BEST Conference Center

12:00 p.m. Registration and lunch with exhibitors Neuro‐Ophthalmology & Pediatrics Section

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

1:05 p.m. Thomas Whittaker, MD, 2015 Update on Pseudotumor Cerebri Syndrome

1:30 p.m. Matthew Recko, MD, Pediatric Uveitis

1:55 p.m. Anna Berry, MD, Efficacy of High Dose Infliximab for the Treatment of Uveitis in Children: A Retrospective Chart Review Anterior Segment & Orbito‐Plastics Section

2:05 p.m. Paul Munden, MD, Neovascular Glaucoma: Management in the Anti‐VEGF Era

2:30 p.m. Emily Broxterman, MD, Bleb Needle Revision with 5‐Fluorouracil: The KU Eye Experience

2:40 p.m. Michelle Boyce, MD, A Retrospective Review of Baerveldt Implants with Tubing 2:50 p.m. BreakInsert Modification to Reduce Post‐Operative Hypotony

3:20 p.m. Robert Null, MD, Osseous Tumors of the Orbit: A Case Presentation

3:30 p.m. Jason Sokol, MD, Trends in Orbital Decompression Surgery

3:55 p.m. Introduction of Dr. Fry: Martin Mainster, MD

4:00 p.m. Luther L. Fry, MD, Distinguished Lemoine Alumnus Lecturer, Standard Cataract Surgery: Tips & Tricks Learned after 40,000+ Cases

5:00 p.m. Session Adjourns On site reception immediately following

University of Kansas Department of Ophthalmology and The Lemoine Alumni Society

Kansas EyeCon May 8 – 9, 2015

Saturday, May 9, 2015

7:30 a.m. Breakfast with exhibitors

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

8:05 a.m. Alina Dumitrescu, MD, Seeing the Light: A Review of the Current State of Treatment for Blinding Inherited Retinal Disorders

8:15 a.m. R.C. Andrew Symons, MD, PhD, Diabetic Macular Edema: An Update

8:45 a.m. Anjulie Quick, MD, Role of Dexamethasone Intravitreal Implant in the Treatment of Persistent Uveitic Macular Edema Secondary to Multiple Sclerosis

8:55 a.m. Ajay Singh, MD, Fluid Under the Retina: Age Related Macular Degeneration or Central Serous Retinopathy

9:20 a.m. Martin Mainster, MD, Photic Retinal Injuries: Light’s Dark Side

9:50 a.m. Lillian Yang, MD, Outcomes of Patients with Macular Edema Treated with 10:00 a.m. Micropulse Laser Break

Cornea Session

10:30 a.m. Mary Champion, MD, Tear Osmolarity in Diabetic Patients

10:40 a.m. W. Abraham White, MD, Pterygium 2015: History and New Horizons

11:05 a.m. Derek Horkey, MD, A First Look at Fungal Keratitis: A Case Report

11:15 a.m. John Sutphin, MD, Dry Eye Assessment and Management (DREAM) Study

11:40 a.m. John Sutphin, MD, Luther and Ardis Fry Professor and Chairman, Closing Remarks: Future of KU Eye

12:00 p.m. Session Adjourns

University of Kansas Department of Ophthalmology and The Lemoine Alumni Society ABSTRACTS Financial Disclaimer 2015 Update on Pseudotumor • I have no financial interest in any matter Cerebri Syndrome discussed in this presentation.

Thomas J. Whittaker, MS JD MD

2015 Update on Pseudotumor Cerebri Revised Classification and Diagnostic Agenda Criteria for PTCS • Revised classification scheme • New Classification‐‐Umbrella Term “Pseudotumor Cerebri Syndrome”(PTCS) includes both • Revised diagnostic criteria – Primary Pseudotumor Cerebri – With/without presence of papilledema – Secondary Pseudotumor Cerebri – Opening pressure on LP—adults vs children • New criteria for diagnosis – “Same old/same old” modified Dandy criteria: Idiopathic • Initial results of IIHTT—Idiopathic Intracranial Intracranial Hypertension (IIH) Hypertension Treatment Trial – New criteria for cases without papilledema New terminology: no longer benign idiopathic – Diet and Diamox vs Diet and Placebo in treatment • intracranial hypertension of IIH Revised diagnostic criteria for the pseudotumor cerebri syndrome in adults and children, D. Friedman, G. Liu, K. Digre, Neurology 81:1159‐1165 (2013).

PTCS Classification: Secondary PTC

PTCS Classification: Primary PTC • Cerebral venous abnormalities • Medications – Cerebral venous sinus thrombosis – Antibiotics: Tetracycline, – Bilateral jugular vein thrombosis or minocycline, doxycycline, nalidixic surgical ligation acid, sulfa drugs – Middle ear or mastoid infection – Vitamin A and retinoids: – Increased right heart Primary pseudotumor cerebri—same old/same old pressure/Superior vena cava Hypervitaminosis A, isotretinoin, all‐ syndrome trans retinoic acid for promyelocytic – “Idiopathic intracranial hypertension (IIH)” – Arteriovenous fistulas leukemia, excessive liver ingestion – Decreased CSF absorption from – Hormones: Human growth hormone, previous intracranial infection or thyroxine (in children), leuprorelin • Includes patients with obesity, recent weight subarachnoid hemorrhage acetate, levonorgestrel,(Norplant – Hypercoagulable states gain, polycystic ovarian syndrome, and thin system), anabolic steroids children • Medical Conditions – Withdrawal from chronic – Endocrine disorders corticosteroids – Meets modified Dandy criteria of papilledema, – Addison disease – Lithium – Hypoparathyroidism – Chlordecone normal neuroimaging, elevated intracranial – Hypercapnia – Sleep apnea pressure on LP, and normal CSF – Pickwickian syndrome – Anemia – Renal failure – Turner syndrome – Down syndrome Diagnosis of pseudotumor cerebri syndrome without Required for diagnosis of pseudotumor cerebri papilledema: syndromea In the absence of papilledema, a diagnosis of pseudotumor cerebri syndrome A. Papilledema can be made if: B. Normal neurologic examination except for cranial nerve abnormalities 1. B–E from above are satisfied, and C. Neuroimaging: Normal brain parenchyma without evidence of hydrocephalus, mass, or structural lesion and no abnormal meningeal 2. In addition the patient has a unilateral or bilateral abducens nerve palsy enhancement on MRI, with and without gadolinium, for typical patients (female and obese), and MRI, with and without gadolinium, and In the absence of papilledema or sixth nerve palsy, a diagnosis of pseudo‐ magnetic resonance venography for others; if MRI is unavailable or tumor cerebri syndrome can be suggested but not made if: contraindicated, contrast‐enhanced CT may be used 1. B–E from above are satisfied, and D. Normal CSF composition 2. In addition at least 3 of the following neuroimaging criteria are E. Elevated lumbar puncture opening pressure (>250 mm CSF in adults satisfied: and >280 mm CSF in children [250 mm CSF if the child is not sedated and – i. Empty sella not obese]) in a properly performed lumbar puncture – ii. Flattening of the posterior aspect of the globe – iii. Distention of the perioptic subarachnoid space with or without a a. A diagnosis of pseudotumor cerebri syndrome is definite if the patient fulfills tortuous optic nerve criteria A–E. The diagnosis is considered probable if criteria A–D are met but – iv. Transverse venous sinus stenosis the measured CSF pressure is lower than specified for a definite diagnosis.

Initial results of the IIHTT IIHTT Initial Results IIHTT: a multicenter, double‐blind, randomized, placebo‐ controlled study of acetazolamide in subjects with mild • 38 sites in North America enrolled 161 women and 4 visual loss. men from March 2010 to November 2012 with follow up ending June 2013. Subjects had to meet the modified Dandy criteria for IIH • Randomized to supervised diet either with and be aged 18 60, and have: ‐ acetazolamide or matching placebo 1. reproducible mild visual loss (−2 to −7 dB perimetric mean deviation [PMD]), • Study drug‐‐acetazolamide 250 mg, two tabs twice a 2. bilateral papilledema, day, with dosage increase of one tab/week up to 4 3. elevated CSF opening pressure, grams daily 4. be untreated with regard to IIH, and 5. no secondary cause of increased intracranial pressure • Subjects evaluated at screening, baseline, and present. 1,2,3,4,5,and 6 months after baseline

Study method details may be found in JAMA 311(16):1641‐51 (2014).

Baseline Symptoms in IIHTT Baseline Visual Field Defects in the IIHTT Results: papilledema IIHTT improvement

IIHTT results: PMD improvement WHAT HAVE WE LEARNED FROM THE IIHTT: 1. Acetazolamide in IIH patients with mild visual loss produces a modest improvement in PMD over six months, much greater with moderate to high grade papilledema.

2. Acetazolamide has its greatest effect on visual field function and papilledema in the first month of escalating dosage.

3. Acetazolamide‐plus‐diet patients lost twice as much weight as placebo‐plus‐diet patients.

4. Risk factors for treatment failure: presence of high grade papilledema, lower ETDRS visual acuity measures at baseline, being Caucasian male. Treatment with the maximally tolerated dosage of acetazolamide appears to substantially reduce the risk of reaching IIHTT criteria of treatment failure.

5. IIH patients on acetazolamide as the only diuretic do not need potassium supplementation.

6. Perimetry performance failures were common—Dr. Keltner’s “bad hair days”‐‐so repeat HVFs if it doesn’t make sense.

7. Perimetric mean deviation is an excellent measure for follow‐up.

Summary • Classification scheme has changed: – Umbrella term is Pseudotumor Cerebri Syndrome Resources: – Good ol’ PTC is now IIH or Primary PTC Wall, M, McDermott, MP, Kieburtz, KD, et al. Effect of acetazolamide – Secondary PTC associated with various medications, on visual function in patients with idiopathic intracranial medical conditions and venous abnormalities hypertension and mild visual loss: the idiopathic intracranial • Diagnostic criteria changed a little hypertension treatment trial. JAMA. 2014;1641‐1651. – Good ol’ PTC=IIH=same modified Dandy criteria Friedman, DI, McDermott, MP, Kieburtz, K, et al. The Idiopathic • Note opening pressure‐‐25 cm adults, 28 in children Intracranial Hypertension Treatment Trial: Design Considerations and Methods. J Neuroophthalmol. 2014. – PTCS without papilledema: different criteria require 6th nerve palsy or MRI abnormalities Wall, M, Kupersmith, MJ, Kieburtz, KD, et al. The Idiopathic Intracranial Hypertension Treatment Trial: Clinical Profile at Baseline. • IIHTT JAMA Neurology. 2014. – Diamox works in larger doses, is safe, and well tolerated Keltner, JL, Johnson, CA, Cello, KE, et al. Baseline visual field findings – Risk for treatment failures in the Idiopathic Intracranial Hypertension Treatment Trial (IIHTT). – Role for surgery/cerebral sinus stenosis stenting not yet Invest Ophthalmol Vis Sci. 2014; 55:3200‐3207. evaluated

Efficacy of High Dose Infliximab for the Treatment of Uveitis in Children: A Retrospective Chart Review

Anna Berry, MD, Resident Class of 2016 Primary Supervisor: Erin Stahl, MD

Uveitis is uncommon in the pediatric population. It is classically thought that the majority of pediatric uveitis is posterior, followed in descending order by anterior, intermediate and then panuveitis. A common etiology of pediatric uveitis is idiopathic, but it is also associated with juvenile idiopathic arthritis (JIA), and other autoimmune diseases.

Topical and systemic glucocorticoids are commonly used to treat pediatric uveitis but are associated with side effects such as cataracts and glaucoma. Alternate “steroid sparing” therapies, including Methotrexate and TNF-alpha blockers, have been explored to limit these unwanted steroid related side effects. This retrospective review evaluates the efficacy of high dose, 20mg/kg, Infliximab in the treatment of pediatric uveitis at Children’s Mercy Hospital in Kansas City, Missouri.

References

Edelsten, Clive, “Uveitis” Pediatric Ophthalmology and Strabismus, New York: Elsevier, 2005. 377- 392.

Pediatric Ophthalmology and Strabismus, Section 6. Basic Clinical Science Course, AAO. 2013- 2014.

Pediatric Uveitis Pediatric Uveitis Educational Objectives 1. Describe the standard systemic work-up for new-onset Matt Recko, MD pediatric uveitis Pediatric Ophthalmology Fellow 2014-2015 Children’s Mercy Hospital and Clinics 2. List the common etiologies for pediatric uveitis Erin Stahl, MD 3. Review steroid-sparing agents for the treatment of Assistant Clinical Professor University of Kansas, Department of Ophthalmology pediatric uveitis

Assistant Professor University of Missouri, Kansas City, Department of Ophthalmology

© The Children's Mercy Hospital, 2014. 03/14 2 © The Children's Mercy Hospital, 2014. 03/14

Initial Ophthalmology Pediatric Uveitis at CMH Assessment • Patients present either due to visual complaint or • Location of Inflammation by referral (rheumatology) for screening – Anterior, Intermediate, Pars Planitis, Posterior, Panuveitis, Scleritis • May initially be seen by an MD or OD

• On initial diagnosis of intraocular inflammation, • Magnitude of Inflammation the patient is referred to rheumatology for – Vision loss, glaucoma, cataract, synechiae, systemic work-up (often on the same day) band keratopathy

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Initial Ophthalmology Initial Ophthalmology Assessment Assessment • What about little kids? • Other testing – Most kids 3 and older can become comfortable with a – IOP every visit slit lamp exam (it may take a few visits) – Baseline macular OCT in all patients (who can – Helpful to have a distracting toy over the examiner’s cooperate) shoulder – Patience • If a sufficient exam is not possible and uveitis is suspected then EUA

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• Anterior uveitis: • Posterior or Panuveitis: – Initially treated with prednisolone acetate 1% 4-8 – Initially treated with oral prednisone 1- times a day depending on degree of inflammation 2mg/kg/day (can give in suspension) – If dosing compliance is a substantial issue then difluprednate 0.05% 2-4 times a day can be – If significant anterior inflammation then add considered (significant IOP rise in children) topical prednisolone 1% QID – Cycloplegia (Atropine 1% BID or cyclopentolate 1% TID)

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Initial Rheumatology Exam Initial Laboratory Testing • Detailed family and past medical history •CBC •Lysozyme •BMP •RPR • Detailed physical exam with special • ESR • Quantiferon Gold attention to skin and joints • Lyme (with travel hx) • Urinalysis • Targeted laboratory studies • ANA •CMV • HLA-B27 • Toxocara • • Toxoplasma ACE level

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First Follow-up Treatment Paths

• Topical/Oral steroids for 1-3 weeks before 1. Rapid improvement – Negative Labs re-examination depending on severity – Begin steroid taper and watch every 2-3 weeks • Check IOP – After tapered from steroids continue to • Check inflammation monitor q 3 months for recurrent inflammation • Check laboratory results – No need to refer to uveitis clinic

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2. Minimal Improvement – Negative Labs 2. Minimal Improvement – Negative Labs – Increase steroid dosing – When improvement seen, slowly taper steroids – Add oral steroid to topical – Consider sub-Tenon triamcinolone injection – If inflammation returns or if unable to control (under general anesthesia in OR) or change with steroids then refer to uveitis clinic to Durezol if compliance is in question – start methotrexate (1mg/kg – max 25) in – Continue to follow every 1-2 weeks until injectable form improvement seen

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Treatment Paths Treatment Paths

3. Positive Labs (30-40% of cases) 3. Positive Labs (30-40% of cases) – Refer to uveitis clinic – Address the underlying cause – Address the underlying cause • Elevated ACE/lysozyme – CXR, evaluate for systemic sarcoid, start MTX • +ANA – joint exam at every visit, continue to treat uveitis as in idiopathic cases • Abnormal urinalysis – need biopsy to rule out TINU, treat TINU with steroids and MTX • +HLA-B27 – typically uveitis is aggressive and difficult to control, will often start MTX at time of • Infectious causes (CMV, Lyme, Syphilis, Toxo) – positive lab test refer to ID for systemic treatment, uveitis managed with systemic/topical steroids as needed, may need MTX

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Uveitis Clinic Uveitis Clinic

• ½ day clinic every other week at the Broadway • Eye tech and rheum nurse work up each patient ophthalmology clinic • Room is darkened for an eye exam • 1 Pediatric ophthalmologist and 1 pediatric rheumatologist see each patient together • Rheumatologist then performs a joint exam

• ~12 patients seen per week (75-100 active • Decisions are made based on these two exams patients) • The format of this clinic allows for excellent • See all patients requiring systemic communication between the ophthalmologist, immunosuppression for uveitis the rheumatologist and the family

17 © The Children's Mercy Hospital, 2014. 03/14 18 © The Children's Mercy Hospital, 2014. 03/14 Next Step - MTX MTX - Risks

• For patients uncontrolled or relapsed after topical • Labs must be monitored q 3 months (CBC, BMP) steroids, MTX is started at 1mg/kg/day (injectable) • Most common complication is elevated liver • MTX takes 6-12 weeks to become therapeutic and to enzymes see a clinical response • Liver ultrasound often reveals fatty liver unrelated • During that time sub-Tenon steroid injections are an to MTX option to lessen systemic steroid load • MTX must be discontinued for persistent elevation • Steroids are continued at the lowest possible doses to • Decreases ability to fight infections control inflammation • Teratogenic, cannot be mixed with alcohol

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Next Step – MTX Failure Next Step – Anti-TNF

• If steroids cannot be weaned or if inflammation • Remicade (infliximab) and Humira recurs after stopping steroids >12 weeks on MTX (adalimumab) are the two most common then the patient is not sufficiently controlled on MTX anti-TNF-alpha agents used to treat • 50% of children with idiopathic and JIA associated pediatric uveitis uveitis are not controlled on MTX alone • Humira is injectable with q 2 week dosing • At this point an anti-TNF-alpha drug is considered and Remicade is given as a 3 hour infusion monthly at an infusion center

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Anti-TNF-alpha agents Anti-TNF-alpha agents Remicade and Humira Remicade and Humira • These medications are both used off-label • Risks: for uveitis although the FDA has recently – Decreased ability to fight infections, latent issued a letter supporting the use of infections (TB, fungal, viral) may reactivate Humira for uveitis – Small long term risk for secondary • Studies show that these two drugs are the malignancies when used in children and most effective for treating uveitis adolescents (lymphoma and T-cell)

– Both of these are black box warnings

23 © The Children's Mercy Hospital, 2014. 03/14 24 © The Children's Mercy Hospital, 2014. 03/14 Anti-TNF-alpha agents Anti-TNF-alpha agents Remicade and Humira Remicade and Humira • Dosing: • Very difficult to get insurance approval as these drugs are used off-label and are very expensive – Humira is prepackaged at 10, 20 and 40 mg based on weight, can be titrated up to weekly • After starting the drugs, clinical improvement is but the dose is not adjusted usually seen within 1 month

– Remicade is given by infusion and started at • At that time steroids are weaned 10mg/kg q 4 weeks, can be increased to 15mg/kg • 80-90% success in steroid-free suppression with the combination of MTX and anti-TNF agents

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Definition of Clinical Non-Responders Response/Control • The 10% of children who do not respond • No anterior segment cell (1-2/HPF tolerated) to MTX and anti-TNF drugs have limited • No active pars planitis options • No macular edema – Can switch anti-TNF drugs • No optic nerve edema – Cyclosporin, mycophenolate, Orencia • Off of all topical and systemic steroids (abatacept) – Some centers tolerate 2 or less drops of prednisolone – Re-evlauate diagnosis (Fuchs) daily in the definition of control

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What Comes Next Relapse

• After stopping steroids and achieving clinical control of • ~50% of children tapered off of inflammation, the child is examined in uveitis clinic every immunosuppressant drugs will have recurrent 3 months inflammation • After 18-24 months without active inflammation, the need for steroids, or active joint disease, systemic • After medication is tapered they continue to be immunosuppression is slowly tapered examined every 3-4 months

• Patient will taper either MTX or anti-TNF first • Recurrent inflammation will restart the process

• Slow taper of all medication can last 6-12 months • Many patients have relapsed multiple times

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• With early diagnosis and aggressive systemic • We believe that aggressive, steroid-sparing systemic treatment of pediatric uveitis is the key to preventing ocular complications immunosuppression, most devastating consequences of pediatric uveitis can be • The short-term risk of systemic medications like MTX and anti-TNF agents is low avoided • The long-term risk of systemic medications like MTX and anti-TNF – Cataract, glaucoma, band keratopathy, CME, retinal agents is largely unknown atrophy, optic nerve atrophy are all complications of uveitis that can be vision threatening • The cooperation of ophthalmology and rheumatology of these cases lessens the fear and barriers for sufficient treatment by both groups – Amblyopia is another potential cause of vision loss in the pediatric population • We look forward to participating in future trials to advance the care of pediatric uveitis patients

31 © The Children's Mercy Hospital, 2014. 03/14 32 © The Children's Mercy Hospital, 2014. 03/14 Neovascular Glaucoma   Elevated Intraocular Pressure

 New vessels on iris and in the angle

Paul M Munden, MD, MBA  Associated findings Associate Professor of Ophthalmology  Hyphema Department of Ophthalmology  Ectropion uveae KU Medical Center  Corneal edema Weiss, et al. PubMed: 13999715, 1963

Neovascular Glaucoma NVG: Associated Conditions    Aggressive, difficult to treat, poor visual outcomes  More Common  Retinal Vein Occlusion  Proliferative Diabetic Retinopathy  Associated with severe underlying systemic and  Carotid Occlusive Disease ocular pathology.  Ocular Ischemic Syndrome

 Understanding pathogenesis key to adequate  Less Common treatment  Central Retinal Artery Occlusion  Ischemia  Chronic Retinal Detachment  Angle status  Intraocular malignancies

Aqueous Humor Dynamics Aqueous Humor Dynamics in NVG

 IOP is a balance between aqueous humor   Fibrovascular membrane and PAS decrease trabecular outflow  Production  2.5 µliter/min  Inflammation may decrease aqueous production  Outflow  Decrease in outflow >> decrease in inflow

 Markedly increased IOP. Aqueous Humor Dynamics in NVG NVG: Pathogenesis    Ischemia from underlying ocular condition

 Induction of vasoproliferative mediators including vascular endothelial growth factor (VEGF)

 Neovascularization of iris and angle

 Growth of fibrovascular membrane across the angle

 Synechial angle closure

NVG: Evaluation NVG: Gonioscopy    At-risk systemic and ocular conditions  NV angle  Higher index of suspicion  Pink flush to “red velvet”  Early identification and treatment  Early fine vessels  Measure IOP  Vessels crossing trabecular meshwork  Distinguish from circumferential vessels  Prior to dilation (even with normal IOP)  Old blood in inferior angle  Careful examination of pupil margin and iris  Gonioscopy  NVA  Peripheral Anterior Synechiae  Synechial angle closure

NVG: Evaluation NVG Treatment Strategy    Opaque medium  Control the intraocular pressure

 Cornea – lower IOP to improve view  Stromal and microcystic edema  Mitigate existing neovascularization  Compression on gonioscopy  Anterior chamber paracentesis  Treat ischemic stimulus to neovascularization  Vitreous  Hemorrhage  B-scan NVG: Control IOP NVG: Medical Therapy    Protect the optic nerve  Topical agents  Extremely elevated IOP  Beta-Blockers  Pre-existing POAG  CAI (dorzolamide, brinzolamide)  Vasculopath  Alpha adrenergic agonists  Prostaglandin analogue  Control Pain  Combination agents  Timolol-brimonidine (Combigan)  Improve vision  Dorzolamide-timolol (Cosopt)  IOP dependent corneal edema  Brinzolamide-brimonidine (Simbrinza)

NVG: Medical Therapy NVG: Surgical Therapy    Oral Carbonic Anhydrase Inhibitor  Trabeculectomy  Acetazolamide, methazolamide  Glaucoma Tube-shunt Implant  Topical Corticosteroid/Cycloplegic  Inflammation  Cyclodestruction  Hyphema  ? Increased non-conventional aqueous outflow  Medical therapy inadequate  Early IOP control  Until neovascular control established  Often temporizing  Long-term IOP control  Synechial angle closure  Setting of synechial angle closure

NVG: Trabeculectomy NVG: Trabeculectomy    Immediate short-term IOP control  5-Fluorouracil (Prospective subgroup 34 eyes)  Median filter survival 38 months  35% patients NLP  Marginally effective long-term IOP  <50 years of age, Type 1 DM increased risk of failure control Tsai, Feuer, Parrish, Grajewski, PubMed: 7777295, 1995

 Chronic inflammation  Mitomycin C (Retrospective 101 eyes)  Vascular permeability  1-year success: 63%, 5-year success: 52%   Aqueous inflammatory mediators Younger age, previous vitrectomy increased risk of failure  Bleb scarring and failure  Fellow eye with NVG Takihara, et al, PubMed: 19195639, 2009 NVG: Tube-Shunt Implant NVG: Surgical Therapy    Baerveldt (Retrospective 36 eyes)  MMC Trabeculectomy vs Ahmed(Retrospective, 40 eyes)  IOP control 79% @ 1 year, 56% @ 18 months  Ahmed success 70% @ 1 year, 60% @ 2 years  31% NLP  Trabeculectomy success 60% @ 1 year, 55% @ 2 years  11% tube occlusion with fibrovascular tissue.  No significant difference (40 eyes, ?power) Sidoti, et al, Pubmed: 9121760, 1995 Shen, et al, Pubmed: 21468334, 2011

 Ahmed (Retrospective 76 patients)  Ahmed success 62% @ 1 year, 21%@ 5 years  24% NLP including patients with IOP control Netland, Pubmed:20126506, 2009

NVG: Surgical Therapy NVG: Laser Therapy    Complications  Transcleral CCP/ Cryotherapy  Hyphema   Filter, tube, or valve occlusion by clot Eyes with little or no visual potential  Place tube superiorly  Pre-surgical administration of bevacizumab  Difficult to titrate treatment effect  Filter/tube failure  May require multiple treatments  Fibrous proliferation from proteins, neovascular growth factors  High risk of hypotony/phthisis  Optic nerve “snuff”  Very high IOP  50% loss of 2 or more LogMAR lines  Vasculopaths Pokroy, et al. PubMed: 18254347, 2008

NVG: Mitigate Existing Remember, It’s Glaucoma! Neovascularization    Long-term patients with multiple ocular and  Treatment role of anti-angiogenic agents continues to systemic issues. be defined  Management with multiple specialists  Consistent follow-up glaucoma examinations  Rapid regression of new vessels on iris and in angle  Baseline and follow-up testing  Visual field testing  Regression temporary and recurrence likely  NFL imaging  Stereo disc photos  Anti-VEGF agents inadequate as mono-therapy  Central corneal thickness NVG: Bevacizumab NVG: Bevacizumab    Early diagnosis and treatment with bevacizumab  Administration after PAS formation may improve outcomes  Minimal to no IOP lowering effect  Angle status at time of diagnosis  93% requiring tube-shunt procedure vs 17% with open angles   Administration prior to PAS formation and angle Wakabayashi, et al PubMed: 18440643, 2008 closure  Long-term surgical rates and outcomes similar with  IOP control without surgery adjunctive use  Geith, et al PubMed:17900231, 2007  Kang, et al PubMed: 24186000, 2013  Delayed requirement for tube-shunt procedure  Olmos and Lee PubMed:21633236, 2011  Moraczewski, et al PubMed:19074917, 2009

NVG: Control Ischemic Stimulus NVG: Control Ischemic Stimulus    Prevention is the best cure!  MOST CRITICAL!  Associated systemic and ocular conditions  Reduces ischemic stimulus  Improves long-term outcomes  Diabetic control  Prevents recurrence of neovascularization  Can prevent NVG  Careful observation of patients at risk  Pupil margin prior to dilation  Retinal ablation (PRP, endolaser, cryotherapy)  Gonioscopy

Neovascular Glaucoma NVG: Summary

Clear Media Opaque Media

Vitreous Open Closed Cataract  Angle Angle Opacity  High index of suspicion in at risk patients

Normal Elevated Open Closed Open Closed IOP IOP Angle Angle Angle Angle  Careful pupil and angle examination.

PRP PRP IVB  Prompt therapy based on pathophysiology IVB FP/GDI  Retinal ablation Phaco Medical Phaco PPV+ECP  Anti-VEGF IVB PPV+ECP PRP IVB IVB FP/GDI IVB  IOP Control IVB PRP 2 weeks FP/GDI PRP 2 weeks  Many go blind!  Follow-up and glaucoma testing IOP YES NO Observation Controlled FP/GDI ?

Bleb Needle Revision with 5-Fluorouracil: The KU Eye Experience

Emily Broxterman, MD, Resident Class of 2015 Primary Supervisor: Paul Munden, MD

Introduction: Surgical management is often necessary in patients with medically uncontrollable glaucoma. Trabeculectomy and implantation of glaucoma drainage devices (such as Ahmed valve or Baerveldt devices) are the most common surgical glaucoma procedures. While these surgeries usually have a high success rate, post-operative complications can occur. One common cause of post-operative drainage failure and increased intraocular pressure is encapsulated bleb formation.

When encapsulate bleb formation and increased intraocular pressure occurs, the surgeon is faced with few options: repeat glaucoma surgery, increase medical therapy or perform bleb needle revision. Bleb needle revision aims to lyse the subconjunctival fibrosis that interferes with successful aqueous drainage and is often augmented with antifibrotic agents such as 5- Fluorouracil. The advantage of needle revision is that it is less invasive than repeating glaucoma surgery and therefore less likely to provoke more scarring. Some studies have also shown it to be more successful than chronic use of topical medications. It has been theorized that the long term use of topical medications with preservatives can lead to increased fibroblast and immune cell activation and therefore increase likelihood of bleb scarring.

Previous studies have evaluated the outcomes of bleb revision with 5-Fluorouracil in patients with underlying glaucoma. We aim to examine the outcomes of slit lamp bleb revision performed at the KU Eye Clinic and identify variables associated with both successful and unsuccessful bleb revisions.

Purpose: 1. To assess the outcomes of bleb needle revision with adjuvant 5-Fluorouracil at the KU Eye Clinic 2. To identify factors associated with both successful and unsuccessful bleb revisions

Methods: A retrospective review was preformed of all patients at the KU Eye Clinic who had undergone bleb needle revision with adjuvant 5-Flurouracil performed at the slit lamp during an office visit over the past two years. A total of twelve patients were identified by searching the CPT code 66250 “Revision of Anterior Segment Wound.” Overall success of bleb revision was evaluated by identifying pre- and post-procedure intraocular pressure measurements as well as the need for additional glaucoma medications. The following information was also evaluated and correlated with success of the bleb revision procedure: Patient age, race, age of onset of glaucoma, mechanism of glaucoma, previous ocular surgeries, compliance history, systemic illnesses and other ocular comorbidities.

Bleb Needle Revision with 5-Fluorouracil: The KU Eye Experience, continued

Emily Broxterman, MD, Resident Class of 2015

References:

1. Tatham A, Sarodia U, Karwatowski W. 5-Fluorouracil Augmented Needle Revision of Trabeculectomy: Does the Location of Outflow Resistance Make a Difference? J Glaucoma. 2013;22:463-467 2. Bae K, Suh W, Kee C. Comparative Study of Encapsulated Blebs Following Ahmed Glaucoma Valve Implantation and Trabeculectomy with Mitomycin-C. Korean J Ophthalmology. 2012;26(4):265-270 3. Kawai M, Yamaguchi T, Nakabayashi S, et al. Combined Baerveldt Glaucoma Drainage Implant Surgery and Surgical Bleb Revision for Preventing a Postoperative Hypertensive Phase. Clinical Ophthalmology. 2014;8:773-776 4. Suzuki R, Susana-Jr R. Early Transconjunctival Needling Revision with 5-Fluorouracil Versus Medical Treatment in Encapsulated Blebs: A 12-Month Prospective Study. CLINICS. 2013;68(10):1376-1379. 5. Zheng L, Arvind H, Wechsler D. Outcomes: Trabeculectomy with Bleb Needle Revision with 5-Fluorouracil. J Glaucoma. 2015;00;00 6. Amini H, Esmaili A, Zarei R, et al. Office-Based Slit Lamp Needle Revision With Adjunctive Mitomycin-C for Late Failed or Encapsulated Filtering Blebs. Middle East African Journal of Ophthalmology. 2012;19(2):216-221

A Retrospective Review of Baerveldt Implants with Tubing Insert Modification to Reduce Post-Operative Hypotony

Michelle Boyce, MD, Resident Class of 2016 Primary Supervisor: Paul Munden, MD

Purpose: Baerveldt implants are an established surgical option for the control of intraocular pressure in selected patients with glaucoma. In two comparative studies with 3 year follow-up Baerveldt implants were shown to have a lower failure rate and require fewer medicines for IOP control compared to Ahmed implants. (1,2) However, Baerveldt implants were shown to have equal or worse complication rates than Ahmed implants, most often associated with hypotony. We experimentally modeled and theoretically analyzed the IOP control properties of the Baerveldt implant. We then predictably modified the system with the insertion of various materials into the tubing outflow system to prevent low pressures. The resulting experimental data was utilized to modify existing surgical techniques with the insertion of suture material into the Baerveldt tubing system to reduce early post-operative hypotony and the associated surgical complications.

Methods: In the experimental model, Poiseuille’s equation was used to calculate the reduction in internal diameter of the Baerveldt implant tubing necessary to yield a target pressure of 5 - 15 mmHg in the tubing outflow system. Various materials were inserted into the tubing outflow system and the resultant pressures were predictably measured. The data was utilized to modify the existing surgical technique for Baerveldt implants with the insertion of suture material into the tubing system. A retrospective chart review was completed.

Results: 13 eyes in 11 patients, ages 84 to 16, underwent the modified Baerveldt tube shunt surgery with insertion of suture material into the tubing system. Over a follow-up period of 1 to 7 months, only 1 patient required surgical management for a hypotony related complication. Post- operative day 1 intraocular pressure ranged from 2 to 21 with no flat anterior chambers noted. At month post-operatively, the intraocular pressure ranged from 6 to 24. Only 4 patients continued to require topical intraocular pressure lowering medications over the post-operative follow-up period.

Conclusions: The pressure modulating effects of the Baerveldt tubing inserts of varying materials and diameters can be predictably modeled. The existing Baerveldt surgical technique can be modified by the insertion of various suture materials into the tubing outflow system. This modification is effective in reducing the occurrence of early post-operative hypotony related surgical complications.

References: 1. Ophthalmology 2014; 121:1547-1557. 2. Ophthalmology 2013; 11: 2232-2240.

Osseous Tumors of the Orbit: A HPI Case Presentation  14 y.o. Caucasian male referred for surgical evaluation

 8 months prior: c/o intermittent diplopia

 6 months prior: reported acute episode of bilateral orbital and facial edema with Robert Null, MD, Class of 2017 presentation to ED Primary Supervisor: Jason Sokol, MD May 8-9, 2015  ED evaluation attributes edema to allergic Kansas EyeCon 2015 reaction, treated with antihistamines

HPI History

 Left orbital edema persists after other facial  PMH Medications edema resolves  Heart Murmur Zyrtec PRN  Patient is referred to ENT for further  Unremarkable Allergies evaluation, then to oculoplastics service at KU developmental course Penicillin G  At presentation at KU patient notes gradual increasing unilateral “eye swelling” since initial  PSH episode  None reported

 Accompanied by morning diplopia but no  POH vision loss or pain  None reported

Voluntary Exam Exam

 VA sc: 20/15 OD 20/20 OS  External: WNL OD, proptosis with projection of globe lateral and inferior with fullness of orbit  VF full OU and resistance to retropulsion OS, no  Pupils: 4/4, 4+/4+, no RAPD lagophthalmos or ptosis

 IOP: 14 OD, 16 OS  Exophthalmometer: base 107, 15 OD, 21 OS

 Motility: left XT and hypoT in primary gaze, full  Anterior exam otherwise benign OD, -2 elevation and -1 all other directions OS Ddx for proptosis • Infectious MRI • Benign Mass • Orbital Cellulitis • Lipoma • Abscess • Pleomorphic adenoma • Inflammatory • Neurofibroma • TED • Meningioma • IOIS • Mucocele

• Vascular • Malignant Mass • Varices • Rhabdomyosarcoma

• Hemangioma • Neuroblastoma

• Hemorrhage • Retinoblastoma • C/C fistula • Fibrous histiocytoma

• Congenital • Adenoid cystic carcinoma

• Dermoid • Craniopharyngioma • Encephalocele

CT1 CT2 Ddx for bony orbital mass Clinical Course

  Osteoma Patient taken to OR for planned resection of  Fibrous dysplasia mass, combined  Osteoblastoma superior orbitotomy and endonasal approach  Osteosarcoma  Liberation of mass from  Paget Disease medial orbital wall and  Giant Cell Granuloma orbital roof into superior orbit, reduced in size  Ewing's Sarcoma prior to removal  Chondrosarcoma

Specimen Post operative course

 Removed dense, bony  Immediate post operative VA CF OS, no RAPD, mass with smooth, motility stable OS, pain well controlled corticated surface  Observed overnight with unremarkable discharge next  Sent to pathology for morning permanent section  5 day post op: 20/40 OS, still XT but only -0.5 in upgaze OS, UL ptosis and V1 numbness OS  Final report: benign ivory osteoma  3 week post op: VA OS to 20/20 with improving ptosis composed almost and V1 numbness entirely of cortical bone,  3 month post op: EOM full OU, ptosis resolved, no atypia or malignancy exophthalmometer base 107, 17 OU

Osteoma Osteoma Clinical Presentation

 Bosselated, round to oval tumors which project from  M:F 1.6-1.8:1 subperiosteal surface of cortical bone  Most commonly asymptomatic (incidental CT  Most commonly originate from frontal or ethmoid bones (secondary) with growth into orbit but cases of findings, though estimated 5% cause symptoms) primary orbital growth reported  Presenting symptoms depend on anatomy but  Ivory (cortical only), mature (trabecular bone), or include headache/pain, metamorphopsia, vision loss, mixed diplopia, epiphora, sinusitis, rarely seizures

 Slow growing over course of months to years  On exam may see proptosis, strabismus, globe (1.6mm/year) displacement

 Between 1-5% progress from sinuses to invade orbit Imaging Management  Benign lesions but clinically significant when causing  CT is imaging method of choice obstruction  Impingement on eye or orbital structures  Dense, sclerotic, well defined and circumscribed mass, often polypoid appearance  Obstruct sinus cavity   Helps to differentiate from osteosarcoma May also involve oral cavity or cranial vault, latter (“sunburst” appearance), osteoblastoma (sclerotic can lead to seizures rim with cystic center), and fibrous dysplasia  Also generate cosmetic concerns (homogenous but irregular and poorly-defined  Surgical excision by oculoplastic surgeon or ENT, margins). specimen to pathology to rule out more aggressive  Note origin of osteoma and proximal structures tumors

(commonly involve superior oblique)  Multiple osteomas associated with Gardner Syndrome

References

th  Kanski, J and Bowling, B. Clinical Ophthalmology: A Systemic Approach. 7 edition. 2011, Elsevier Ltd.

th  Kumar, V et al. Pathologic Basis of Disease. 8 Edition. 2010, Elsevier Inc.

 Basic and Clinical Science Course, Section 4. 2014, American Academy of Ophthalmology.

 Mansour, A et al. Ethmoid Sinus Osteoma Presenting as Epiphora and Orbital Cellulitis: Case Report and Literature Review. Survey of Ophthalmology. 1999; 43 (5): 413-26.

 Wei, L et al. Orbital Osteoma: Clinical Features and Management Options. Ophthal Plast Reconstr Surg. 2014; 30 (2): 168-74.

 Bilkay, U et al. Benign Osteoma With Gardner Syndrome: Review of the Literature and Report of a Case. J Craniofac Surg. 2004 May;15(3):506-9.

 Turri-Zannoni, M et al. Frontoethmoidal and Intraorbital Osteomas Exploring the Limits of the Endoscopic Approach. Arch Otolaryngol Head Neck Surg. 2012 May; 138 (5): 498-504.

 McHugh, J et al. Sino-Orbital Osteoma: A Clinicopathologic Study of 45 Surgically Treated Cases With Emphasis on Tumors With Osteoblastoma-like Features. Arch Pathol Lab Med, 2009 Oct; 133: 1587-93. Background 1911: Dollinger first described surgical orbital decompression using the lateral orbitotomy approach. 1930: Hirsch and Urbanek removed the orbital floor 1931: Naffziger described transcranial approach to orbital roof Jason A Sokol, MD removal Assistant Professor 1936: Sewall removed medial orbital wall for decompression 1957: Walsh and Ogura developed the combined removal of Director, Oculofacial the orbital floor and medial wall Plastic & Orbital Surgery 1973: Fat decompression of orbit first proposed by Crawford KU Eye 1985: Kennedy describes endoscopic approach 1989: Leone first describes deep lateral wall decompression 1998: Shepard proposes a balanced medial and lateral wall approach

Background Background 1911: Dollinger first described surgical orbital decompression 1911: Dollinger first described surgical orbital decompression using the lateral orbitotomy approach. using the lateral orbitotomy approach. 1930: Hirsch and Urbanek removed the orbital floor 1930: Hirsch and Urbanek removed the orbital floor 1931: Naffziger described transcranial approach to orbital roof 1931: Naffziger described transcranial approach to orbital roof removal removal 1936: Sewall removed medial orbital wall for decompression 1936: Sewall removed medial orbital wall for decompression 1957: Walsh and Ogura developed the combined removal of 1957: Walsh and Ogura developed the combined removal of the orbital floor and medial wall the orbital floor and medial wall 1973: Fat decompression of orbit first proposed by Crawford 1973: Fat decompression of orbit first proposed by Crawford 1985: Kennedy describes endoscopic approach 1985: Kennedy describes endoscopic approach 1989: Leone first describes deep lateral wall 1989: Leone first describes deep lateral wall decompression decompression 1998: Shepard proposes a balanced medial and lateral wall 1998: Shepard proposes a balanced medial and approach lateral wall approach

Question/Problem Objective  Multiple techniques for orbital decompression  Ascertain what technique is preferred by current  No consensus in literature on preferred or best members of the American Society of Ophthalmic technique Plastic and Reconstructive Surgery (ASOPRS) in performing orbital decompression for Graves' disease. Results Methods 1. Years of experience performing  Ten question survey sent to ASOPRS listserv orbital decompression N = 91  All questions multiple choice with option to leave comments  Statistical analysis of answers  Correlation with years of surgical experience  Likelihood of collaboration with ENT

2. What approach is preferred? 3. Technique for medial wall

3. Technique for medial wall 4. Technique for floor

Of the 19 individuals who use a transnasal endoscopic approach 18 of 19 perform with ENT (p < 0.05). 6. Technique for deep lateral wall 5. Technique for lateral wall decompression

7. Fat decompression 8. Orbital strut:

 Majority rarely remove orbital strut, remove in cases of optic nerve compression or severe proptosis

9. Reason for decompression 10. ENT involvement 10. ENT involvement‐ 25% Conclusion  Years of experience did not correlate significantly (p =  Orbital decompression is an evolving surgery and no 0.299) one technique is universally adopted by members of  Endoscopic approach for medial wall, almost exclusively ASOPRS performed in collaboration with ENT (p < 0.05)  Surgical approach is tailored to specific patient’s needs  Less likely to remove fat at time of decompression if  If use endoscopic approach, almost exclusively perform surgery with ENT (p = 0.003) performed in collaboration with ENT

Further questions  Should endoscopic approach be taught to ASOPRS surgeons?  Other factors to consider in preferred technique:  where individual trained  how many decompressions performed in training and how many currently performing  practice in academic or private setting  region of practice  Which approach provides the best results while minimizing side effects  Can a study be designed to determine the standard of care Effect of Differing Ocular Hypotensive Drops Immediately After Cataract Surgery on 3 and 24 Hour Post‐Op IOP Luther L Fry, MD; Eric Fry, MD NO Financial Garden City, Kansas E Randy Craven, MD Disclosures

Baltimore, Maryland / Riyadh, Saudi Arabia

180 Consecutive Cataract Surgery Patients Were Randomized To The Following Groups: 1. Combigan • Drops were given Exclusions: 2. Cosopt immediately at the end of cataract 3. Trusopt surgery. 1. Glaucoma 4. Timoptic 0.5% • Pressures were 2. Inability to return for 24 5. Lumigan checked by hour post‐op pressure check 6. Pilocarpine 2% Goldmann Applanation at 3 and 3. Asthma 7. Betoptic‐S 24 hours post‐op. 8. Alphagan‐P 0.1% Pressures above 35 received a side‐port 9. Control (Artif Tear) “burp”.

RESULTS (20 pts/group): CAI Study (Phase I) Drug Pre‐Op 3 Hrs “Burps” 24 Hrs (20pts per group) Cosopt 14.4 16.4 (0) 0% 14.3 Combigan 15.6 17.2 (0) 0% 14.4 Timolol 0.5 15.7 19.6 (1) 5% 17.3 DRUG Pre‐Op 3 Hrs “Burp” 24 Hrs Trusopt 14.3 22.7 (1) 5% 14.0 Dorzolamide 15.9 23.4 (3) 15% 15.9 Alphagan P 14.8 22.7 (1) 5% 14.9 Azopt 15.8 28.9 (5) 20% 14.1 Pilo 2% 16.4 25.5 (2) 10% 17.7 Trusopt 16.4 30.4 (7) 35% 16.7 Art Tear 14.1 27.9 (3) 15% 16.9 Art Tear 16.7 34.0 (10) 50% 14.5 Betoptic‐S 16.3 29.7 (5) 25% 16.6 Diamox 15.9 34.8 (12) 60% 17.5 Lumigan 15.1 29.7 (5) 25% 16.9 500 mg Seq CAI Phase II (20 Pts/Group) Best Effective Drug Study (Fellow Eye As Control) Pre 3 Hrs “Burps” 24 Hrs 30 patients, 60 eyes Trusopt 16.0 24.4 (4) 20% 15.9 Bilateral Cats Needing Surgery—Fellow Diamox 500mg Seq 15.8 24.4 (2) 10% 13.1 Eye used as control: Azopt 16.6 24.9 (5) 25% 17.1 First Eye Randomized to Combigan Dorzolamide 16.9 25.9 (5) 25% 16.7 Dx 250mg Two Tabs 16.2 28.8 (6) 30% 17.0 (10), Cosopt (10), Pilo 4% (10), or Tears Control (Art Tears) 15.3 29.1 (9) 45% 18.3 (30), Second eye two weeks later randomized to Active Med or Control

2013 STUDY (20/Group) RESULTS DRUG Pre‐Op 3 Hrs “Burp” 24 Hrs Cosopt 16.0 16.7 (0) 0% 14.7 Drug Pre‐Op 3 Hrs “Burps” 24 Hrs Combigan 15.9 18.4 (2) 10% 17.1 Dorzolamide 17.3 19.7 (1) 5% 17.2 Diamox 500mg Sequel 13.8 20.9 (3) 15% 14.2 Cosopt 16.7 19.9 (1) 10% 17.1 Timolol 0.5 15.9 20.9 (2) 10% 16.7 Brimonidine 15.3 21.4 (1) 5% 15.5 Alphagan P 0.1% 15.9 23.2 (4) 20% 18.8 Combigan 15.8 21.3 (1) 10% 17.6 Pilocarpine 2% 16.6 24.1 (3) 15% 18.2 Azopt 15.2 24.2 (3) 15% 15.2 Pilo 4% 15.0 24.0 (1) 10% 15.2 Diamox 250 mg Two Tabs 15.7 24.5 (5) 25% 15.2 Trusopt 15.6 24.8 (5) 25% 14.9 Betoptic‐S 14.6 25.7 (6) 30% 17.2 Art. Tears 16.3 27.6 (6) 20% 16.3 Control (Artificial Tear) 14.6 27.9 (5) 25% 17.9 Pilocarpine 4% 15.3 28.3 (6) 30% 15.8 Lumigan 16.6 28.3 (6) 30% 15.6

Simbrinza Study ‐ 2014 Simbrinza Study Results 100 patients enrolled (20 patients/group). Drug Pre-Op 3 Hrs “Burps” 24 Hrs Cosopt 14.95 14.55 (0) 0% 14.05 Results: Simbrinza is effective in management of IOP in the immediate post‐operative period, Combigan 15.60 14.90 (0) 0% 13.05 though Cosopt and Combigan continue to perform best. Simbrinza 16.75 17.50 (1) 5% 16.90

One patient (Combigan) had a 3‐hour IOP of Pilocarpine 4% 16.00 23.95 (2) 10% 18.60 5mmHg. Art. Tears 16.75 27.05 (4) 20% 15.55 Historical Data – Culmination of All Studies (790 patients) Drug Pre-Op 3 Hrs “Burps” 24 Hrs Cosopt ‐ N = 70 15.3 16.4 (1) 1% 14.7 Combigan ‐ N = 70 15.7 17.5 (3) 4% 15.2 Simbrinza ‐ N = 20 16.8 17.5 (1) 5% 16.9 Timolol 0.5% ‐ N = 39 15.8 20.3 (3) 8% 17.0 Brimonidine (Generic Alphagan) ‐ N = 20 15.3 21.4 (1) 5% 15.5 Alphagan P 0.1% ‐ N = 40 15.4 23.0 (5) 13% 17.0 Dorzolamide (Generic Trusopt) ‐ N = 56 16.8 23.2 (9) 16% 16.5 Pilocarpine 2% ‐ N = 40 16.5 24.8 (5) 13% 18.0 Trusopt ‐ N = 63 15.6 25.7 (13) 21% 15.5 Pilocarpine 4% ‐ N = 50 15.5 25.7 (8) 16% 16.8 Azopt ‐ N = 52 15.8 26.8 (12) 23% 15.5 Betoptic‐S ‐ N = 40 15.4 27.7 (11) 28% 16.9 Artificial Tears ‐ N = 123 15.8 28.9 (35) 28% 16.3 Lumigan ‐ N = 41 15.8 29.0 (10) 24% 16.3 Diamox 250 mg x ii ‐ N = 25 16.4 30.0 (9) 36% 17.7 Diamox 500 mg Sequel x I ‐ N = 41 15.8 30.1 (16) 39% 15.3

SUPRISES Low IOP • Pilo 2% & 4% minimally better than Nine patients (1% of cumulative total) with control (Probably Blocked by Midriacyl) 3‐Hr IOP less than 5mmHg: – Azopt (1 patient) • Lumigan NO better than control – Betoptic‐S (1 patient) (Probably takes a couple of weeks) – Combigan (1 patient) – Diamox 500mg Sequel (1 patient) • Systemic CAI no better than topical CAI – Dorzolamide (1 patient) (Maybe “roughed up” epithelium allows – Pilocarpine 2% (1 patient) better penetration of topical CAI) – Timolol 0.5% (1 patient) – Trusopt (2 patients) • Generics as good, or better than brand name

SO‐‐‐‐ THANK YOU! Based on these studies we now use Generic Cosopt for non‐asthmatics, Luther Fry, MD Simbrinza for asthmatics and NO Eric Fry, MD Systemic CAIs (No Better Than E Randy Craven, MD Topical, so Why Put Up With Questions? Systemic Side Effects?) [email protected]

Seeing the Light: A Review of the Current State of Treatment for Blinding Inherited Retinal Disorders

Alina Dumitrescu, MD, Resident Class of 2015 Primary Supervisor: Ajay Singh, MD

• Inherited eye disorders are among the most common causes of pediatric blindness in the United States and usually manifest early in life. This is a review of current recommendations for genetic testing for diagnosis of affected individuals and family members at risk to have affected offspring.

• Until very recently, genetic causes of blindness have been untreatable. Gene replacement therapy delivered to the retina by subretinal injections show promise for treatment for some of these disorders. We review the reported results and ongoing trials using gene therapy for inherited retinal disorders at this moment.

Diabetic Macular Edema: An Update

R. C. Andrew Symons, MD, PhD

Pathophysiology of diabetic macular edema (DME)

Early Treatment of Diabetic Retinopathy Study (ETDRS) laser for diabetic macular edema - Treatment - Effects - How can visual function be optimized in patients treated with laser?

Triamcinolone - Comparison with laser treatment - Effect in pseudophakia - Risk of raised intraocular pressure

VEGF inhibition: vision, retinal sensitivity, treatment burden - Comparison with laser treatment - The DRCR comparison of aflibercept, ranibizumab and bevacizumab - Is placental growth factor involved in DME pathogenesis? - What effect does VEGF inhibition have on retinal non-perfusion? - What effect does VEGF inhibition have on progression of diabetic retinopathy? - Is there a rebound effect when VEGF inhibition is withdrawn? - What is the effect of VEGF inhibition on hard exudates? - What are the other anatomical effects of VEGF inhibition? - If VEGF inhibition helps DME, then does PRP help DME in the long term?

Steroid implants - Visual acuity - Longevity of effect - Intraocular pressure rise

What is the evidence for changing from one VEGF inhibitor to another? For changing from VEGF inhibition to steroid? For combining VEGF inhibition and steroid?

What are the predictive factors for visual function after treatment of diabetic retinopathy? What is the best prophylactic treatment at the time of cataract surgery?

Unanswered questions: Is there still a role for laser treatment of center involving clinically significant macular edema (CSME)? Is there still a role for laser treatment of non-center involving CSME? Is there a role for subthreshold laser treatments? Is there a role for retinal surgery in DME?

Role of Dexamethasone Intravitreal Implant in the Treatment of Persistent Uveitis Macular Edema Secondary to Multiple Sclerosis

Julie Quick, MD, Resident Class of 2017 Primary Supervisor: Ajay Singh, MD

Purpose:

To describe our experience in treating recalcitrant cases of cystoid macular edema (CME) in patients with pars planitis in the setting of Multiple Sclerosis (MS) with the dexamethasone (DEX) intravitreal implant (Ozurdex; Allergan, Inc, Irvine, CA).

Methods:

A retrospective chart review was done analyzing five eyes from three patients with a history of MS diagnosed with pars planitis and persistent non-infectious uveitic CME who were treated with DEX 0.7 mg intravitreal implant. All patients had previously been treated with different forms of steroid therapy prior to DEX implant. Spectral domain optic coherence tomography (SD-OCT) and fluorescein angiography (FA) were used to diagnosis CME and pars planitis. Visual acuity, central macular thickness on OCT, intraocular pressure, and subjective improvement in quality of vision were analyzed.

Results:

All five eyes showed improvement in central macular thickness and visual acuity within one month of DEX implant.

Conclusion:

A single DEX implant showed improvement in patients with persistent uveitic CME in the setting of MS and pars planitis and may be a good adjunctive treatment to other forms of ocular immunosuppressive therapies.

Fluid Under the Retina: Age Related Macular Degeneration or Central Serous Retinopathy

Ajay Singh, MD Assistant Professor

Central serous chorioretinopathty (CSC) and exudative age related macular degeneration (AMD) can both present with central neurosensory detachments. In a minority of CSC patients, the disease develops into a chronic condition with atrophy of photoreceptors and significant drop in visual acuity. To distinguish between CSC and AMD in cases where both show leaking on angiography, other signs are helpful, such as ‘gutter’ tracks, retinal precipitates and the absence of drusen.

This talk discusses clinical features and investigations that may help in differentiating between the two conditions, as the management is very different. In small lesions, the physician is unable to make the correct diagnosis of the underlying disease. Newer modalities, such as fundus autofluorescence (FAF) and enhanced depth imaging (EDI), that assist in making a diagnosis in these two conditions will be discussed.

Photic Retinal Injuries: Light’s Dark Side

Martin Mainster, Ph.D., M.D., FRCOphth

Educational objectives 1. To summarize photomechanical, photothermal and photochemical retinal injuries. 2. To explain why retinal chromophore absorption spectra are clinically significant. 3. To review countermeasures for clinical and industrial photic retinal injuries.

Summary Light can damage the retina by photomechanical, photothermal (photocoagulation) and photochemical (phototoxicity) mechanisms. Ophthalmologists seldom treat people with real or specious photic retinal injuries. Understanding light’s chorioretinal effects is valuable for evaluating and managing these patients and dealing with the occupational and legal issues that can ensue. Photomechanical retinal effects occur when extremely high chorioretinal temperatures cause local tissue distortion and hemorrhage. In the past, most photomechanical retinal trauma was caused by laboratory research lasers and military rangefinders or target designators. High powered consumer lasers resembling laser pointers now produce a growing number of injuries, especially in children and young adults. The location and extent of chorioretinal trauma and vitreous hemorrhage determine initial visual loss. Blood can spread laterally in sub-hyaloid, subretinal or sub-RPE spaces. Chorioretinal scars form and evolve. Vision may improve over days to months. Prognosis is excellent for injuries that do not involve the fovea. Macular holes may close and choroidal neovascularization (CNV) may resolve spontaneously but conventional macular hole surgery and CNV therapy are valuable when needed. Photothermal retinal injuries are usually caused by pulsed laser exposures that range in duration from a microsecond to a few seconds. Industrial and military photothermal laser accidents are less common than photomechanical ones, because they require a narrow range of retinal irradiances high enough for photocoagulation but too low for photomechanical tissue distortion. Retinal burn severity is determined by the magnitude and duration of chorioretinal temperature elevation, lesion size, fundus pigmentation and chorioretinal sequellae. Photo- thermal and photomechanical retinal trauma is managed similarly. Injuries should be followed for retinal holes and CNV that may develop within a few months of the injury. Photochemical retinal trauma (also known as photic retinopathy or retinal phototoxicity) is caused by intense light exposures lasting seconds to minutes that would probably be well tolerated if experienced only momentarily. Illuminances far exceed normal environmental light levels but chorioretinal temperature elevations are too low for photothermal damage. Optical radiation produces highly reactive oxygen radicals that can damage retinal cell membranes, proteins, carbohydrates and nucleic acids. The most common signs of acute retinal phototoxicity are small yellowish-white foveolar lesions in solar or welding arc maculopathy and larger, sometimes extrafoveal lesions, in operating microscope or endoilluminator injuries. Photic retinopathy can be divided into photosensitizer- and photopigment-mediated phototoxicities which have different action spectra. The hazardousness of photosensitizer- mediated retinal phototoxicity increases rapidly with decreasing wavelength, similar to the

Photic Retinal Injuries: Light’s Dark Side, continued Martin Mainster, Ph.D., M.D., FRCOphth

absorption spectrum of lipofuscin in the retinal pigment epithelium which is its primary mediator. Thus, in acute exposures, UV radiation is much more hazardous than visible light and blue light is more hazardous than longer wavelengths. Therapeutic photochemical effects with and without exogenous photosensitizers are termed photodynamic therapy and photostimulation, respectively. Appropriate protective measures are available for solar and welding arc maculopathies. Minimizing the intensity and duration of operating microscope and endoilluminator exposures reduces injury risk. The potential role of environmental light exposure in AMD remains unproven but ultraviolet radiation is implicated in cataractogenesis and possibly ocular melanoma so it is prudent to wear sunglasses and a brimmed hat in bright environments such as beaches and skiing slopes.

Conclusion Accidental laser injuries are preventable with protective eyewear. Clinical retinal photocoagulation does not cause chronic pain and neither do accidental retinal laser injuries. Visual abnormalities from an alleged laser injury should be well correlated with chorioretinal abnormalities. Powerful handheld lasers that appear identical to laser pointers are retinal photocoagulators. The only common clinical photochemical injuries are solar or welding arc maculopathies and operating microscope or endoilluminator injuries. Solar maculopathy can occur with or without sungazing. People under 30 years of age are at greatest risk to solar and welder’s maculopathy because of the UV-B window in their crystalline lenses.

References Mainster MA, White TJ, Tips JH, Wilson PW: Retinal-temperature increases produced by intense light sources. J Opt Soc Am 1970; 60:264-70. Mainster MA. Spectral transmittance of intraocular lenses and retinal damage from intense light sources. Am J Ophthalmol 1978; 85:167-170. Mainster MA, Ham WT, Jr., Delori FC: Potential retinal hazards: instrument and environmental light sources. Ophthalmology 1983; 90:927-32. Mainster MA. Laser light, interactions and clinical systems. In: L'Esperance FA Jr., ed. Ophthalmic Lasers, 3rd ed. St. Louis: C.V. Mosby Co, 1989; Chapter 3, pp. 61-77. Mainster MA, Sliney DH, Marshall J, Warren KA, Timberlake GT, Trokel SL. But is it really light damage? Ophthalmology 1997; 104:179-180 Mainster MA. Decreasing retinal photocoagulation damage: principles and techniques. Seminars Ophthalmol 1999; 14:200-209. Mainster MA, Stuck BE, Brown J Jr. Assessment of alleged retinal laser injuries. Arch Ophthalmol 2004; 122:1210-17. Mainster MA, Boulton M: Retinal phototoxicity, Chapter 174, in Albert DM, et al., eds: Principles and Practice of Ophthalmology. London, Elsevier, 2008, ed. 3rd, pp. 2195-205. Mainster MA, Turner PL. Blue-blocking IOLs decrease photoreception without providing significant photoprotection. Surv Ophthalmol 2010; 55:272-83. Mainster MA, Turner PL. Retinal examination and photography are safe…is anyone surprised? Ophthalmology 2010; 117:197-8. Mainster MA, Turner PL. Photic retinal injuries: mechanisms, hazards and prevention. In: Ryan SJ, ed. Retina, 5th ed. London: Elsevier, 2013; Vol 2, Chapter 90, pp. 1555-63.

Outcomes of Patients with Macular Edema Treated with Micropulse Laser

Lillian Yang, MD, Resident, Class of 2016 Primary Supervisor: Ajay Singh, MD

Micropulse laser therapy has been shown by many clinical trials to be effective in the use of retinal vascular disease including diabetic retinopathy. With conventional laser treatments, there is iatrogenic retinal damage and functional loss. The development of the diode laser with micropulsed emission has allowed subthreshold therapy without a visible burn endpoint. This reduces the risk of structural and functional retinal damage, while retaining therapeutic efficacy. Subthreshold micropulse diode laser photocoagulation is designed to target the RPE while minimizing the negative thermal effects on the neural retina and deeper structures. Laser photocoagulation decreases the intraocular concentrations of vascular endothelial growth factor and other angiogenic growth factors, thereby inhibiting active retinal neovascularization.

The purpose of this study is to evaluate outcomes of patients that underwent micropulse laser at the University of Kansas Department of Ophthalmology to assess efficacy and determine if any relationships exist that promote better or worse outcomes.

Tear Osmolarity in Diabetic Patients

Mary Champion, MD, Resident, Class of 2015 Primary Supervisor: Ajay Singh, MD

Diabetes mellitus is associated with many ophthalmic complications, including diabetic retinopathy, cataract formation, orbital infections, oculomotor palsies and ocular surface disease. Ocular surface disease is more prevalent in the diabetic population than in the general population.1,2 Studies of diabetic patients have shown changes in tear osmolarity,3 tear composition4 and tear film stability,2,5 decreased reflex tearing,6 decreased corneal sensation,7,8 conjunctival squamous metaplasia and loss of goblet cells.5,6 Most of the ocular surface alterations reported in diabetic patients seems to be secondary to decreased corneal sensitivity7,8 and the presence of ocular dryness. Decreased corneal sensitivity and decreased sensory input may decrease basal and reflex tear secretion, and perhaps also damage autonomic nerve fibers regulating the lacrimal gland.9-11 A contributing factor to dry eye in diabetic patients may be damage to the posterior ciliary nerves from laser panretinal photocoagulation (PRP) used for treatment of proliferative diabetic retinopathy. PRP arrests and causes regression of neovascularization, but also damages the retina and underlying ciliary nerves. This decreases corneal sensitivity and potentially leads to a worsening of ocular surface disease. Studies have shown mixed results, and have suggested that PRP may alter the corneal subbasal nerve plexus12,13 and corneal sensitivity.7,14,15 PRP has also been associated with increased risk for tear dysfunction and ocular surface disease.16

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

Our study objective is to determine if tear osmolarity in diabetic patients could be correlated to factors, such as duration of disease, severity of retinopathy or history of previous PRP. Results of the research can give insight into the course of ocular surface disease in diabetics, particularly those patients with proliferative diabetic retinopathy requiring PRP.

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. Grus FH, Sabuncuo P, Dick HB, Augustin AJ, Pfeiffer N. Changes in the tear proteins of diabetic patients. BMC Ophthalmology. 2002;2:4. 5. Dogru M, Katakami C, Inoue M. Tear function and ocular surface changes in noninsulin- dependent diabetes mellitus. Ophthalmology. Mar 2001;108(3):586-592.

Tear Osmolarity in Diabetic Patients, continued

Mary Champion, MD, Resident, Class of 2015

6. Goebbels M. Tear secretion and tear film function in insulin dependent diabetics. The British Journal of Ophthalmology. Jan 2000;84(1):19-21. 7. Rogell GD. Corneal hypesthesia and retinopathy in diabetes mellitus. Ophthalmology. Mar 1980;87(3):229-233. 8. Rosenberg ME, Tervo TM, Immonen IJ, Muller LJ, Gronhagen-Riska C, Vesaluoma MH. Corneal structure and sensitivity in type 1 diabetes mellitus. Investigative Ophthalmology & Visual Science. Sep 2000;41(10):2915-2921. 9. 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. 10. Acosta MC, Peral A, Luna C, Pintor J, Belmonte C, Gallar J. Tear secretion induced by selective stimulation of corneal and conjunctival sensory nerve fibers. Investigative Ophthalmology & Visual Science. Jul 2004;45(7):2333-2336. 11. 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. 12. De Cilla S, Ranno S, Carini E, et al. Corneal subbasal nerves changes in patients with diabetic retinopathy: an in vivo confocal study. Investigative Ophthalmology & Visual Science. Nov 2009;50(11):5155-5158. 13. 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. 14. Schiodte SN. Effects on choroidal nerves after panretinal xenon arc and argon laser photocoagulation. Acta Ophthalmol (Copenh). Apr 1984;62(2):244-255. 15. Ruben ST. Corneal sensation in insulin dependent and non-insulin dependent diabetics with proliferative retinopathy. Acta Ophthalmol (Copenh). Oct 1994;72(5):576-580. 16. Ozdemir M, Buyukbese MA, Cetinkaya A, Ozdemir G. Risk factors for ocular surface disorders in patients with diabetes mellitus. Diabetes Research and Clinical Practice. Mar 2003;59(3):195-199. 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.

The Fine Print

Pterygium 2015: • I will discuss off-label use of devices for History and New Horizons pterygium surgery • I have no financial interest in any of the technologies presented W. Abraham White, MD • But I do really enjoy pterygium surgery! Clinical Assistant Professor University of Kansas Medical Center

Pterygium

• Pathogenesis • Name derived from Greek – pterygion • Techniques “little wing” •Adjuvants • Fibrovascular ingrowth into the • Antimetabolites superficial cornea • Fibrin Glue • Highly correlated with UV exposure • New Concepts • Frequency increases with proximity to the equator

Pathogenesis Pterygium Surgery

• Factors such as TGF-β and VEGF known • Many complications of surgery are to be elevated possible, but the most common with all • Growth can cause irritation, induce techniques is recurrence of disease astigmatism, and obscure vision, if it • Risk factors for recurrence include encroaches on the visual axis young age, dark pigmented skin, incomplete resection Surgical Techniques Bare Sclera

•Bare Sclera • Historically popular • Primary Closure • Quick and simple •Flap Closure • Recurrence rates in some series exceed •Autografting 50% • Amniotic Membrane Graft • Performance seems to be better if combined with an antimetablite

Primary Closure Flap Closure

• Like bare sclera excision, is relatively • Scleral defect is covered by sliding or quick and simple rotating adjacent tissue • Recurrence rate averages ~50% • Reported recurrence rates vary substantially • Many approach 5-10% range • Likely dependent on surgeon factors • Could be a reasonable technique for smaller defects

Conjunctival Autograft Limbal Autograft

• First described by Kenyon and • Limbal stem cells grafted into the colleagues in 1985 (5.3% recurrence pterygium defect rate) • Thought to accelerate healing • Free graft is taken from elsewhere on • Reconstruction may limit fibrous the eye and affixed to the defect proliferation • Numerous methods for attaching the • Recurrence rates generally very low graft have been described (<5% range) Amniotic Membrane Graft 5-Fluorouracil (5-FU) • Pyrimidine analog antimetabolite • Acellular membrane applied to wound • Interferes with DNA/RNA replication bed • Has been used preoperatively and • Recurrence rates with AM alone ~20%. intraoperatively to prevent recurrence • Use of adjuvants reduces risk to range • Recently reported for postoperative comparable to CAG treatment of recurrence • Useful technique when conservation of conjunctival tissue is critical (glaucoma, extensive scarring)

Mitomycin C Mitomycin C

• Antibiotic isolated from Streptomyces • Associated with many significant caespitosus adverse effects • Selectively inhibits DNA synthesis at low • Corneal/scleral melts concentrations • Limbal stem cell deficiency • Inhibits RNA and protein synthesis at •Glaucoma higher concentrations • Cataract • Used in pterygium, glaucoma, and even • Side effects and cost have limited strabismus surgery widespread use and acceptance

Fibrin Glue Pre Op

• Purified from pooled human plasma • Thrombin and fibrinogen components separated • Mixed together in a syringe or on the eye • Risk of transmission of blood borne pathogens • Use of autologous blood has been suggested and performed Post Op (1 month) Post Op (6 months)

New Concepts PERFECT Excision

•PERFECT excision • Pterygium Extended Removal Followed • Anti-VEGF drugs by Extended Conjunctival Transplant • 20% Ethanol • Described by Hirst • Postoperative 5-FU to treat recurrence • Recently published a prospective series of 1000 consecutive patients

PERFECT Technique PERFECT Results

• Pterygium amputated at limbus, • 1000 consecutive procedures stripped from cornea • 1 recurrence • Tenon’s dissected free from conjunctiva • Complications and sclera from limbus to caruncle/just • Transient diplopia for 2-7 days inside superior/inferior recti and excised • “Moderate pain” leaving bare sclera 14 mm x 14 mm • Perilimbal free conjunctival graft sutured to cover wound bed PERFECT Criticisms Anti-VEGF drugs

• Procedure >1 hour for primary cases • Popularly used for ARMD and DME (and • High learning curve a whole host of other things) • Unforgiving tolerances • Injection and topical therapy used • Has not yet been replicated by other • Used pre- and postoperatively surgeons

Anti-VEGF Drugs 20% Ethanol excision

• Most trials utilize bevacizumab • Reported by Tsumi et al. • Lots of small studies • 20% ethanol used to loosen pterygium • May decrease recurrence from cornea • Will not induce complete regression • Mitomycin C also used after recurrence has started

20% Ethanol Protocol 20% Ethanol Results

• 3-4 drops applied to a pterygium using • 68 eyes in 64 patients a metal well for 40 seconds • No intraoperative complications • Pterygium bluntly dissected • Recurrence rate 2.9% with minimum 12 • Mitomycin C with conjunctival autograft month follow up (CAG) performed 5-FU for Recurrent Pterygium 5-FU Protocol

• Retrospective study by Said et al. • Increased vascularity + fibrovascular • Weekly 5-FU injections (2.5-5 mg) proliferation x 2 visits = treatment given • Intralesional injections given weekly • 15 eyes/14 patients until no further growth noted • 12 after 1st excision, 3 after 2nd

5-FU results References

• Tsumi E, Levy J, et al. New approach for • Hirst L. Recurrence and complications after pterygium removal using 20% ethanol. Int 1000 surgeries using pterygium extended • 14/15 eyes improved or arrested Ophthalmol 32. 2012; 443-8 removal followed by extended conjunctival • Said DG, Faraj LA, et al. Intralesional 5 transplant. Ophthalmology. 119. 2012; 2205- progression (93.3%) fluorouracil for the management of recurrent 10. pterygium. Eye 27(10). 2013; 1123-9. • Sekeroglu H, Erdem E, et al. Sutureless amniotic • Janson BJ, Sikder S. Surgical management of membrane transplantation combined with • Most patients required 3 injections (max pterygium. The Ocular Surface 12(2). 2014; narrow-strip conjunctival autograft for 112-9. pterygium. Int Ophthal 31. 2011; 433-8. • Aslan L, Aslankurt M, et al. Comparison of wide • Kim M, Chung S, et al. Comparison of mini-flap 8) conjunctival flap and conjunctival autografting technique and conjunctival autograft techniques in pterygium surgery. Journal of transplantation without mitomycin C in primary Ophthalmology 2013; 5 pages (epub). and recurrent pterygium. Ophthalmologica 222. • No major complications, but some • Ozgurhan E, Agca A, et al. Topical application 2008; 265-71. of bevacizumab as an adjunct to recurrent • Enkvetchakul O, Thanathanee O, et al. A patients did have SCH pterygium surgery. Cornea 32(6). 2013; 835-8 randomized controlled trial of intralesional • Shenasi A, Mousavi F, et al. Subconjunctival bevacizumab injection in primary pterygium. bevacizumab immediately after excision of Cornea 30(11). 2011; 1213-8. primary pterygium: the first clinical trial. Cornea 30(11). 2011; 1219-22. A First Look at Fungal Keratitis: A Case Report

Derek Horkey, MD, Resident, Class of 2017 Primary Supervisor: Miranda Bishara, MD

Background

We report a case of fungal keratitis by an organism that has rarely shown to be pathogenic to the Casehuman cornea. Presentation

A 16‐year‐old female with history of contact lens wear who presented with a non‐healing corneal ulcer after a camping trip along Missouri’s Niangua River. The patient was initially treated with anti‐bacterial antibiotics with some initial success followed by a rapid decline in exam. Fungal keratitis was then suspected and the patient was subsequently treated with topical antifungals. The patient’s course was complicated by intraocular pressure uncontrolled by topical medications, inability to identify the microorganism for a significant amount of time, and lack of expected response to therapy. Ultimately, patient received a penetrating keratoplasty, secondary to corneal perforation, as well as need for a tube shunt, secondary to uncontrollable intraocular pressure. ConclusionThe post‐transplant infection was controlled with topical ampho tericin.

Metarrhizium sp.

Ultimately, microorganism was identified as We were able to get the first documented confocal microscopy images of this fungus. This is only the fourth documented case of infection with this fungus and it is the first time when the organism was isolated to the cornea only that natamycin alone did not provide adequate treatment. This case may represent an isolated mutation of this species or provide evidence of the general adaptive abilities of this species previously unknown. Functions of a The Dry Eye Assessment and Management Study Healthy Tear Film  Optical clarity and surface regularity

 Ocular surface comfort - lubrication

 Protection from environmental and infectious insults  Anti-microbial proteins, antibodies, complement John Sutphin, MD  Reflex tears to flush away particles Luther & Ardis Fry Professor & Chairman  Supportive environment for corneal epithelium  Necessary electrolytes, physiological pH and osmolarity Supported by The National Eye Institute National Institutes of Health, Department of Health and Human Services  Protein factors for growth and wound healing Grant Numbers: U10 EY022881 and U10 EY022879

The Healthy Tear Film A Delicate Balance Healthy Tears  Lipid, aqueous & mucin components  A complex mixture of proteins, mucins, and electrolytes  Outer lipid layer prevents aqueous evaporation  Electrolytes for proper  Secreted by meibomian glands osmolarity  Aqueous component – a complex mixture of proteins,  Antimicrobial proteins: mucins, electrolytes Lysozyme, lactoferrin, IgA  Secreted by main & accessory lacrimal glands  Growth factors & suppressors of inflammation: EGF, cytokines  Mucins provide viscosity and stability during the blink cycle  Soluble mucin 5AC secreted by  Mucin gel decreases in density goblet cells provides viscosity toward tear film surface  Membrane-bound mucins 1 & 4 help stabilize tear film Image from Dry Eye and Ocular Surface Disorders, 2004

Tears in Chronic Dry Eye (CDE)  Increased tear osmolarity Dry Eye Definition  Lesser concentrations of many proteins in CDE  DEWS Report (The Ocular Surface, 2007)  e.g., antimicrobial proteins “Dry eye is a multifactorial disease of the tears  Growth factor and ocular surface that results in symptoms of concentrations decreased discomfort, visual disturbance, and tear instability with potential damage to the ocular  Cytokine balance shifted, surface. It is accompanied by increased promotes inflammation osmolarity of the tear film and inflammation of the ocular surface.”  Loss of goblet cells decreases mucin  Inflammation  Tear Film Disorder  Ocular Surface Damage  Due to loss of goblet cells  Affects 14% - 33% of the population  Impacts viscosity of tear film  5 Million Americans over age 50 have dry eye  Activated proteases  Untreated dry eye progresses  Degrade extracellular matrix & tight junctions Dry Eye Disease (DED) Omega-3 Fatty Acids

 May be the most common complaint for office visit  Omega-3 is a polyunsaturated fatty acid  Economic Burden of DED  Named for the location of the first double bond  Medical treatment costs: $700 -$1300 per patient per  Eicosapentaenoic acid (EPA) year  Docosahexaenoic acid (DHA)  For USA, this is ~$3.8 billion per year  Found in: fish, flax seed oil  Productivity losses: $12,000 to $18,000 per patient per year  Has been associated with anti-inflammatory effects in  For USA, this is over $55 billion per year! inflammatory diseases  Rheumatoid arthritis  Significant impact on quality of life, productivity,  Cardiac disease surgical outcomes, and patient satisfaction

Omega-3 and Dry Eye Disease Specific Aims of the DREAM Study

 If DED is an inflammatory disease of the ocular surface  Aim 1: Determine the efficacy and safety of oral and Omega-3 has anti-inflammatory properties … Omega-3 compared to placebo in patients with  Could Omega-3 be used to treat DED? dry eye disease over 1 year

 As of 2014, only 13 randomized controlled trials  : To describe and evaluate a performed using Omega fatty acids in DE patients Aim 2 comprehensive set of features of dry eye disease  13 different treatments (Omega-3 alone, Omega-6 and treatment (signs, symptoms, biomarkers, and alone, Omega-3 + Omega-6) economic factors) over one year of observation  Single site, over 1- 3 months  No consistency in improvement of signs or symptoms  Aim 3: To determine the long term effects of  The jury is still out! Omega-3 essential fatty acids through 2 years  DREAM will provide answers

DREAM Collaborators Clinical Sites

Study Chair Office Coordinating Center Icahn School of Medicine at University of Pennsylvania Mount Sinai School of Medicine

Principal Investigator Principal Investigator Penny A Asbell, MD, MBA, FACS Maureen G. Maguire, PhD

Project Manager Project Directors Brendan Barry, BA Ellen Peskin, MA, CCRP Biomarker Laboratory Kathleen McWilliams, CCRP Seth Epstein, MD Yi Wei , PhD DREAM CLINICAL TRIAL DESIGN Outcome Measures

Primary Secondary Exploratory Candidate •Change in Ocular Surface • Compliance with the study treatment • Contrast Sensitivity Patients Disease Index (OSDI) score protocol as measured by changes in • Signs measured by keratography: 24 Month from baseline blood levels of essential fatty acids  TBUT, TMH, redness, 1/2  Follow-up and pill counts. meibography 12 Month Active 3 Exam Active 3 Follow-up Exam Randomize • Change in Signs of DED (conjunctival • Tear osmolarity and corneal staining, TBUT, • Meibomian gland secretion Schirmer’s test) • Biomarker levels: Randomize 2/3 24 month • Use of artificial tears or other  MMP-9, tear cytokine levels, 1/2 Follow-up Eligible Placebo Exam treatments for DED HLA-DR expression. Patients 1/3 • Quality of life as measured by the SF-  Blood- autoimmune 36 biomarkers Follow-up 12 Month Placebo Exam • Change in Brief Ocular Discomfort Index (BODI) score. • Incidence of ocular and systemic adverse events, changes in VA and IOP • Cost-effectiveness of using Omega-3

Primary Trial Randomized Extension Study (12 months) (12 months)

Eligibility Criteria – Primary Trial Testing

 ≥ 2 of the following 4 signs in the same eye at screening  Tear Break Up Time (TBUT) and baseline visits (same signs) Conjunctival staining present ≥ 1 (out of 6) Evaluate evaporative state Corneal fluorescein staining present ≥ 4 (out of 15) Flourescein and no anesthesia Tear film break-up time (TBUT) ≤ 7 seconds Schirmer’s test ≥ 1 to ≤ 7 mm/5min  Graded Meibomian gland  Ocular Surface Disease Index (OSDI) score: expression 25-80 at screening 21-80 at baseline  Symptoms of DED ≥ 6 months  Use (or desire) of artificial tears ≥ 2 times/day in last 2 wks

Lissamine Green Testing

 Schirmer Test With Anesthetic • Basal secretion

 Impression cytology

 Tear cytokines

 Osmolarity Exclusions Concurrent Dry Eye Treatments  Pregnancy or lactating  Punctal plugs if in place at least 90 days and will  Herpes simplex keratitis or other active keratitis be continued

 Contact lens wear  Only allowed eye drops are lacriserts and artificial tears if commit to the same brand and frequency  Prior lasik or refractive surgery for the next year

 Glaucoma medications or surgery  Doxycycline, autologous serum tears and Restasis if used for 90 days and will continue.  Cataract surgery in the last 6 months Must be off 30 days at time of entry

 Heparin or warfarin  Lipiflow and light therapy are disqualifying unless not used in last 90 days  Certain other conditions

Treatment Assignment Concurrent Dry Eye Treatments

 Systemic steroids and/or immunosuppressants if  Treatments used for at least 90 days at entry and will continue Active supplements at same dose (2000 mg EPA and  Systemic medications associated with causing 1000 mg DHA per day) dryness (anti-depressants, anti-histaminics, etc) Placebo supplements may be continued if they have been used 30 days and will be continued  Patients are randomized to a supplement group

 Lid hygiene should continue in the same manner  2:1 ratio active:placebo throughout the trial  Double masked – patient and evaluators do not  Current supplements of EPA/DHA if less than know treatment assignment 1200 mg per day

Eligibility Criteria – Extension Study Sample Size

 Assigned to active supplements in Primary Trial Primary Trial and willing to continue taking supplements  579 total

 We believe this operational definition will select  386 Active supplements for patients who perceive benefit from their active  193 Placebo supplements supplements

Extension Study  190 total  95 Active supplements  95 Placebo supplements Visit Schedule DREAM

Primary Trial Extension Study  DRy Eye Assessment and Management Study  Screening Visit  Month 15: “Check In” Telephone Call The first major, non-pharmaceutical funded  Month 00: Baseline Visit  Month 18: trial on Dry Eye Disease

 Month 03  Month 21: “Check In” Telephone Call Unique opportunity to study Dry Eye Disease

 Month 06  Month 24 in a well-defined cohort of DE patients  Month 09: “Check In” Telephone Call Will allow us to evaluate the role of Omega-3 in Dry Eye Disease and in ocular inflammatory  Month 12 processes

DREAM Sites and Investigators DREAM Sites and Investigators

Site Number Principal Investigator City Site Number Principal Investigator City 22 11 Milton M. Hom, OD, FAAO Azusa, CA David R. Hardten, MD Minneapolis, MN 23 12 Robert Pendleton, MD Oceanside, CA Joseph Tauber, MD Kansas City, MO 24 13 Meng Lin, OD Berkeley, CA Steven Silverstein, MD Kansas City, MO 25 15 Harvey Dubiner, OD Morrow, GA Penny Asbell, MD New York, NY 26 16 Clark Springs, MD Indianapolis, IN Henry Perry,MD Rockville Center, NY 27 17 Kathleen Kelley, DO Indianapolis, IN Jodi Luchs, MD Wantagh, NY 28 Holly Hindman, MD Rochester, NY 18 John E. Sutphin, MD Prairie Village, KS 29 Vatinee Bunya, MD, Philadelphia, PA 19 Jack V. Greiner, DO, OD, PhD Boston, MA 30 Michael Christensen, OD, PhD Memphis, TN 20 Reza Dana, MD Boston, MA 21 Roni Shtein, MD Ann Arbor, MI

Thank You!

John Sutphin, MD 7400 State Line Rd, Prairie Village, KS 66208 913-588-0105 (Anna Bryan)