Review of Uveitis

BUSINESS, CONSUMER SERVICES, AND HOUSING AGENCY EDMUND G. BROWN JR., GOVERNOR STATE BOARD OF OPTOMETRY 2450 DEL PASO ROAD, SUITE 105, SACRAMENTO, CA 95834 0 P (916) 575-7170 F (916) 575-7292 www.optometry .ca.gov OPToMi fikY

Continuing Education Course Approval Checklist

Title:

Provider Name:

☐ Completed Application Open to all Optometrists? ☐Yes ☐No Maintain Record Agreement? ☐Yes ☐No

☐Correct Application Fee

☐Detailed Course Summary

☐Detailed Course Outline

☐PowerPoint and/or other Presentation Materials

☐Advertising (optional)

☐CV for EACH Course Instructor

☐License Verification for Each Course Instructor Disciplinary History? ☐Yes ☐ No

BUSINESS, CONSUMER SERVICES, AND HOUSING AGENCY EDMUND G. BROWN JR., GOVERNOR 0 OPToMi fikY

Continuing Education Course Approval Checklist

Title:

Provider Name:

☐Completed Application Open to all Optometrists? ☐Yes ☐No Maintain Record Agreement? ☐ Yes ☐No

☐ Correct Application Fee

☐Detailed Course Summary

☐Detailed Course Outline

☐PowerPoint and/or other Presentation Materials

☐Advertising (optional)

☐CV for EACH Course Instructor

☐License Verification for Each Course Instructor Disciplinary History? ☐Yes ☐No

1 BUSINOUMER SEIMCES,AND HOUS;?:a~:~::o~0~~~~~~~~~5. SACRAMENTO, CA 958~0VERNOR EOMU~OWN JR.

0 p~fcj'~{iFrRy p (916) 575-7170 F (916) 575-7292 WWW.Optometry.ca.gov ~

CONTINUING EDUCATION COURSE APPROVAL I :$5(lMa 11_datory Fee -I APPLICATION Pursuant to California Code of Regulations (CCR) § 1536, the Board will approve continuing education (CE) courses after receiving the applicable fee, the requested information below and it has been determined that the course meets criteria specified in CCR § 1536(9).

In addition to the information requested below, please attach a copy of the course schedule, a detailed course outline and presentation materials (e.g., PowerPoint presentation). Applications must be submitted 45 days prior to the course presentation date. Please tvoe or orint clearly. Course Title Course Presentation Date Review of Uveitis

Course Provider Contact Information Provider Name Craig Leong J. (First) (Last) (Middle) Provider Mailing Address

Street 122 La Casa Via, #2?{J City Walnut Creek State CA Zip 94598

P .d E . Add rov1 er ma1 1 ress [email protected]

Will the proposed course be open to all California licensed optometrists? ~YES ONO

Do you agree to maintain and furnish to the Board and/or attending licensee such records of course content and attendance as the Board requires, for a period of at least three years ~YES ONO from the date of course presentation?

Course Instructor Information Please provide the information below and attach the curriculum vitae for each instructor or lecturer involved in the course. If there are more instructors in the course, please provide the reQuested information on a separate sheet of paper. Instructor Name Craig Leong Jan

(First) (Last) (Middle)

License Number G28041 License Type M.D.

Phone Number ( 925 ) 943-6800 Email Address [email protected]

I declare under penalty of erjury under the laws ofthe State ofCalifornia that all the information submitted on this form and o any ompanying attachments submitted is true and correct. 4/17/17 Date Form CE-01, Rev. 5/16 2 Attention Board of Optometry.

To whom it might concern,

Along with this letter you will find CV’s from all three doctors, CE applications, Summaries, Outlines, and

Presentation materials. I apologized for the information being a little late but one of the doctors was

Out of town and I didn’t get his presentation information until much later.

Let me know if you need any other information.

Hedy Rodriguez

Batra Vision Medical Group [email protected]

Uveitis

Uveitis is an autoimmune disease of the eye that refers to a number of intraocular inflammatory conditions. Uveitis can be associated with various systemic diseases and it is important for an eye care provider to recognize the possible ocular manifestations of these systemic conditions

Examples of common anterior, intermediate and posterior uveitis will be presented. Panuveitis as well and the ocular complications of HIV will also be discussed. The etiology, clinical findings, diagnostic testing and treatment of each disease entity will be summarized.

Following this lecture, attendees should be able to recognize the findings, categorize the types and understand how the most common causes of uveitis are currently managed.

4 Definition of Uveitis Overview Classification of Uveitis Granulomatous vs Non-granulomatous Unilateral vs Bilateral Symptoms Ocular findings Standardized Grading Scale for Anterior Chamber Inflammation

Examples of Anterior Uveitis • Traumatic iritis • HLA-B27 • Herpes simplex uveitis • Juvenile Idiopathic Arthritis

Examples of Intermediate Uveitis • Pars Planitis • Multiple Sclerosis • Endophthalmitis

Examples of Posterior Uveitis • Toxoplasmosis

Examples of Panuveitis • Sarcoidosis • Syphilis • Tuberculosis • Vogt-Koyanagi-Harada Disease

Ocular Complications of HIV • HIV Retinopathy • Panuveitis secondary to syphilis and toxoplasmosis • Ocular lymphoma • Fungal Endophthalmitis • Frosted Branch Angiitis • Cytomegalovirus (CMV) Retinitis

Herpes Retinitis • Acute Retinal Necrosis (ARN) • Progressive Outer Retinal Necrosis (PORN)

5 4/24/2017

2 Uveitis: Inflammation of the Uvea

3 Overview • 58/100,000 persons • Whites>non-whites • Genders equally affected (but women outlive men • Increasing prevalence with age • Third leading cause of blindness in the developed countries • 39% of chronic anterior uveitis is truly idiopathic

4 Classification of Uveitis Anterior Uveitis • Iritis: Inflammation of the iris • Iridocyclitis: Inflammation of the iris and ciliary body s Classification of Uveitis Intermediate Uveitis / Pars Planitis • Pars Plana: "Snowbank" inflammatory exudates • Vitreous: inflammatory cells and clumped WBC's in the vitreous

6 Classification of Uveitis Posterior Uveitis • Choroiditis: Inflammation primarily in the choroid, e.g.., Punctate Inner Choroiditis (PIC)

7 Classification of Uveitis Posterior Uveitis • Chorioretinitis: Inflammation of the choroid > retina, e.g., Presumed Ocular Histoplasmosis Syndrome (POHS) a Classification of Uveitis Posterior Uveitis • Retinochoroiditis: Inflammation in the retina > choroid, e.g., Toxoplasmosis retinochoroiditis

g Classification of Uveitis Panuveitis • Inflammation of all of the layers of the uvea, e.g., uveitis secondary to tuberculosis, syphilis, sarcoidosis, Vogt Koyanagi Harada Disease, sympathetic ophthalmia

10 Classification of Uveitis Non-granulomatous • Fine deposits of lymphocytes on corneal endothelium • Etiology: Uveitis secondary to HLA-B27, juvenile idiopathic arthritis, multiple sclerosis, inflammatory bowel disease, psoriasis, systemic lupus erythematosis

11 Classification of Uveitis Granulomatous • Thick deposits of lymphocytes and epithelioid cells on corneal endothelium • Etiology: Uveitis secondary to syphilis, sarcoidosis, tuberculosis, toxoplasmosis, Vogt Koyanagi Harada Disease, herpes zoster/simplex, sympathetic ophthalmia

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12 Unilateral vs. Bilateral Unilateral • Etiology: Infectious, traumatic, post-operative, idiopathic

13 Unilateral vs. Bilateral Bilateral • Etiology: Systemic infection, autoimmune, granulomatous disease

14 Uveitis Symptoms • Blurred vision and ocular pain • Ocular redness / circumlimbal flush • Light sensitivity / photophobia 1s Ocular Findings • Inflammatory cells and flare (protein) in the aqueous • Keratic precipitates on corneal endothelium

16 Ocular Findings • Posterior synechiae (pupillary adhesions to lens) • Iris atrophy (secondary to chronic iritis) • Iris nodules (WBC's on anterior iris stroma)

17 Ocular Findings • Hypopyon (layered WBC's in inferior AC angle) • Inflammatory glaucoma (inflammatory blockage of trabecular meshwork) • Inflammatory hypotony (ciliary body shutdown)

1s Ocular Findings • Cataract (due to inflammation or steroid treatment) • Vitritis: Vitreous inflammation • Pars plana "snowbank" inflammatory exudates

19 Ocular Findings • Chorioretinal inflammation • Retinal vasculitis

20 Ocular Findings • Optic disc hyperemia • Cystoid macular edema

21 Standardized Grading Scale for Anterior Chamber Inflammation

22 Anterior Uveitis: Traumatic Iritis • Etiology: accidental blunt trauma, fist fights, sports injuries, car accidents • 20% of iritis • Findings: cells and flare, hyphema, subconjunctival hemorrhage • Management: cycloplegic and steroid eyedrops

23 Anterior Uveitis: Human Leukocyte Antigen HLA-B27 Uveitis

2 7 4/24/2017

• Associated diseases: Ankylosing spondylitis, reactive arthritis (Reiter syndrome), inflammatory bowel disease, psoriatic arthritis • Incidence: 40-70% of acute anterior uveitis • Findings: AC fibrin, hypopyon, posterior synechiae

24 Anterior Uveitis: Human Leukocyte Antigen HLA-B27 Uveitis • Diagnosis: HLA-B27 blood test • Management: Topical steroid and cycloplegic eyedrops, periocular/intravitreal steroid injections, NSAIDs, systemic steroids, cyclosporine, methotrexate, azathioprine, etanercept (Enbrel)

2s Anterior Uveitis: Herpes Simplex Keratouveitis • Etiology: Herpes simplex virus • Incidence: 9% of anterior uveitis • Findings: 85% anterior> 15% posterior uveitis, decreased corneal sensitivity, iris atrophy, keratic precipitates, posterior synechiae, glaucoma

26 Anterior Uveitis: Herpes Simplex Keratouveitis • Clinical diagnosis: unilateral anterior uveitis with high IOP • Laboratory diagnosis: Negative HSV titer rules out HSV; PCR testing for HSV DNA in the aqueous • Management: cycloplegic and steroid eyedrops, treat glaucoma, oral antiviral medications (Acyclovir, valacyclovir, famciclovir)

27 Anterior Uveitis: Juvenile Idiopathic Arthritis • Etiology: probable autoimmune reaction to ocular antigens with a possible genetic predisposition • Incidence: 6% of uveitis are in children of which the most frequent cause is JIA. 10-20% of JIA patient will develop uveitis • Findings: AC cells with white eye, keratic precipitates, posterior synechiae, band keratopathy, cataract, CME

2s Anterior Uveitis: Juvenile Idiopathic Arthritis • Diagnosis: ANA is positive in 80%, HLA-DRS • Management: Steroid and cycloplegic eyedrops, NSAIDs, systemic steroids, methotrexate, etanercept (Enbrel), infliximab (Remicade), adalimumab (Humira), abatacept (Orencia), tocilizumab (Actemra)

29 Intermediate Uveitis: Pars planitis • Etiology: Autoimmune • Incidence: 10% of uveitis is due to pars planitis • Findings: Vitreous cells, pars plana "snowbank" exudates, retinal vasculitis, CME, cataract, inflammatory glaucoma

30 Intermediate Uveitis: Pars planitis • Diagnosis: Clinical presentation; no specific testing available • Management: Periocular steroid injections, cryopexy of pars plana, vitrectomy+endolaser, treatment of inflammatory glaucoma, cyclosporine, azathioprine, methotrexate, cyclophosphamide

31 Intermediate Uveitis: Multiple Sclerosis • Etiology: Multiple sclerosis

3 8 4/24/2017

• Incidence: 14% of uveitis patients have MS, 27% of MS patients have uveitis • Findings: Retinal vasculitis, CME, vitreous cells, retrobulbar neuritis

32 Intermediate Uveitis: Multiple Sclerosis • Diagnosis: HLA-DR2 antigen, brain MRI scan • Management: Periocular steroid injections, treatment of inflammatory glaucoma, cyclosporine, azathioprine, methotrexate, cyclophosphamide

33 [gJ Intermediate Uveitis: Post-operative Endophthalmitis • Presentation: 3-14 days post-op, progressively worsens • Symptoms: Blurred vision, redness, pain • Incidence: 0.08-0.68% after cataract surgery, 0.2-0.4% after secondary IOL, 0.2-9.6% after glaucoma filter, 0.03-0.05% after vitrectomy

34 Intermediate Uveitis: Post-operative Endophthalmitis • Findings: corneal edema, AC cells and fibrin, hypopyon, vitritis, retinal vasculitis and infectious retinitis • Management: Sample the aqueous / vitreous for culture+sensitivity of organisms, intravitreal injection of vancomycin and ceftazidime, vitrectomy with intravitreal antibiotics if Va is only LP

35 Intermediate Uveitis: Endogenous Endophthalmitis • Endogenous: infection that spreads from body to eye • Associated conditions: diabetes, HIV, IV drug abuse, immunosuppressive therapy, indwelling catheter, recent intravenous infusion • Incidence: 2-8% of endophthalmitis cases

36 [g} Intermediate Uveitis: Endogenous Endophthalmitis • Findings: Infectious retinitis, vitritis • Diagnosis: Culture blood, vitreous and any indwelling catheter for bacteria and fungus • Management: Initiate treatment with intravenous vancomycin and ceftazidime, revise antibiotics depending upon culture results

37 iE] Posterior Uveitis: Toxoplasmosis • Etiology: Toxoplasma gondii, a parasite carried by cats. Intermediate hosts are humans, mammals, birds and reptiles. Most common cause of infectious posterior uveitis

38 g Posterior Uveitis: Toxoplasmosis • Congenital: passed from mother to fetus in utero with later reactivation of scar • Acquired: primarily in immunocompromised patients • Ocular findings: Active retinochoroiditis and vitritis adjacent to a congenital scar; large, confluent and bilateral lesions in immunocompromised patients.

39 Posterior Uveitis: Toxoplasmosis • Diagnosis: Toxoplasma IgM and IgG titers, PCR of aqueous and vitreous • Treatment: Pyrimethamine, sulfadiazine and oral steroids. Alternative treatment regimens include systemic / intravitreal clindamycin, oral Bactrim, azithromycin, atovaquone, intravitreal dexamethasone

4 9 4/24/2017

40 Panuveitis: Sarcoidosis • Etiology: Unknown. Possible genetic and environmental factors. Possible association with HLA-DRB1 antigen and exposure to tuberculosis. • Incidence: 3-10% of all uveitis. African Americans > whites, females>males • Symptoms: blurred vision, redness, floaters, eye pain

41 Panuveitis: sarcoidosis • Ocular findings: conjunctiva!, scleral and lacrimal gland granulomas, granulomatous anterior uveitis, iris nodules, posterior synechiae, cataract, vitritis, choroiditis, retinal vasculitis (candle-wax drippings), CME, optic neuropathy and inflammatory glaucoma

42 Panuveitis: sarcoidosis • Systemic findings: non-caseating granulomas, pulmonary hilar adenopathy, erythema nodosum, lymphadenopathy, arthritis, cough and polymyositis • Diagnosis: serum angiotensin converting enzyme (ACE) and serum lysozyme, chest X ray, chest CT scan, conjunctiva! biopsy, whole body gallium scan

43 Panuveitis: Sarcoidosis • Treatment: Topical steroid and cycloplegic eyedrops, oral steroids, periocular steroid injections, methotrexate, cyclosporine, infliximab (Remicade)

44 Panuveitis: Syphilis • Etiology: STD infection by Treponema Pallidum; Acquired >>Congenital cases • Incidence; <5% of all uveitis cases; high risk sex is the key factor; 67% of acquired cases occur in men who have sex with men; high rate of HIV coinfection

45 Panuveitis: Syphilis • Ocular findings: Iridocyclitis, iris nodules, keratic precipitates, vitritis, multifocal chorioretinitis, retinal vasculitis, CME, optic neuropathy, Argyll Robertson pupil, inflammatory glaucoma • Systemic findings: Genital chancres, skin rash, impaired balance, deafness, dementia, aortic aneurysm

46 Panuveitis: Syphilis • Diagnosis: RPR (Nonspecific) and FTA-ABS (specific), lumbar puncture for CSF cells, protein and VDRL serology • Treatment: Topical steroid and cycloplegic eyedrops • Neurosyphilis: Intravenous Penicillin G x 14 days

47 Panuveitis: Tuberculosis • Etiology: Mycobacterium tuberculosis, an airborne pathogen with primary pulmonary involvement

5 10 4/24/2017

• Ocular findings: granulomatous panuveitis, vitritis, choroiditis, vasculitis, CME and optic neuropathy • Systemic findings: Secondary involvement of the bones, brain, liver, kidneys and heart

48 g Panuveitis: Tuberculosis • Incidence: 3 cases/100,000 people in USA; 1-2% of all cases of uveitis; higher risk in immunocompromised patients, health care workers and immigrants from endemic countries • Diagnosis: PPD skin test, quantiferon gold blood test, chest x-ray, sputum culture, PCR of aqueous/vitreous

49 Panuveitis: Tuberculosis Treatment: • Systemic tuberculosis is treated with rifampin, isoniazid, enthambutol, and pyrazinamide • Ocular manifestations are treated with topical steroid and cycloplegic eyedrops in conjunction with systemic antibiotics so igJ Panuveitis: Vogt Koyanagi Harada Disease • Etiology: Unknown but assumed to be autoimmune • Incidence: 1-3% of uveitis in USA; 7-9% of uveitis in Japan; darker pigmented individuals; women>men • Symptoms: Headache, photophobia, blurred vision, nausea, eye pain s1 Panuveitis: Vogt Koyanagi Harada Disease • Ocular Findings: Choroiditis with multifocal serous retinal detachments, optic disc hyperemia, granulomatous panuveitis, choroidal depigmentation • Systemic Findings: Poliosis (loss of melanin in hair), vitiligo (loss of melanin in skin), alopecia (loss of hair), tinnitus (ringing in ears), dysacusis (loss of hearing)

52 bJJ Panuveitis: Vogt Koyanagi Harada Disease • Diagnosis: Fluorescein and ICG angiography, OCT scan, fundus hyperautofluorescence; lumbar puncture shows CSF pleocytosis (increased WBC's and protein) • Treatment: Systemic corticosteroids, methotrexate, azathioprine, cyclosporine s3 Ocular Complications of HIV • Etiology: HIV incidence (37,600 new cases/year in 2014) declining due to HAART (highly active anti-retroviral therapy. Ocular complications occur in 70-80% HIV patients; increased risk when CD4 count drops to < 200 cells/cubic mm • Ocular Findings: Kaposi's sarcoma, molluscum contagiosum

54 [T7 Ocular Complications of HIV • Ocular Findings: Herpes zoster ophthalmicus, herpes keratitis

55 Ocular Complications of HIV • Ocular Findings: HIV retinopathy, ocular syphilis, toxoplasmosis retinochoroiditis, ocular lymphoma,

56 p Ocular Complications of HIV • Ocular Findings: fungal endophthalmitis

57 Q Ocular Complications of HIV

6 11 4/24/2017

• Ocular Findings: Frosted branch angiitis, cytomegalovirus (CMV) retinitis sa Panuveitis: ARN vs. PORN • ARN: Acute Retinal Necrosis ( not immunocompromised) • PORN: Progressive Outer Retinal Necrosis (immunocompromised or HIV) • Etiology: Herpes (zoster or simplex) retinitis in both conditions

59 fol Panuveitis: ARN vs. PORN • Symptoms: Blurred vision, vitreous floaters, photophobia initially in one eye • Ocular Findings: Rapidly progressive peripheral retinal necrosis with severe panuveitis and occlusive retinal vasculitis, retinal detachment, optic atrophy • Diagnosis: PCR of intraocular fluids for herpes DNA

60 Panuveitis: ARN vs. PORN • Medical therapy: Intravenous acyclovir x 14 days followed by oral valacyclovir x 3 months or longer • Surgical Therapy: Prophylactic laser photocoagulation of large retinal breaks if retina not detached. Vitrectomy with endolaser and silicone oil tamponade if retina is detached.

61 rrdJ Panuveitis: ARN vs. PORN • Medical therapy: Intravenous acyclovir x 14 days followed by oral valacyclovir x 3 months or longer • Surgical Therapy: Prophylactic laser photocoagulation of large retinal breaks if retina not detached. Vitrectomy with endolaser and silicone oil tamponade if retina is detached. 62 [g] The Final Word • History, history, history: Most cases of uveitis have a cause and the patient's medical history will give you the clues to finding it. • Always dilate and examine both eyes: Anterior segment inflammation often has a posterior component that will indicate the cause. • Be wary of simply treating with topical steroids without determining the cause of the uveitis: steroids suppress inflammation, delay making a diagnosis and, in some cases, can allow the underlying condition to worsen.

7 12

BayAreaRetinaAssociates M E D I C A L G R O U P Craig J. Leong, M.D. CURRICULUM VITAE

ALLEN Z. VERNE, M.D. Professional Corporation Born: Dinuba, California, USA 4/19/47 CRAIG J. LEONG, M.D. Professional Corporation College: Stanford University, Palo Alto, CA B.A. in Psychology 1965 - 1969 STEWART A. DANIELS, M.D. Professional Corporation Medical School: Northwestern University, Chicago, IL 1969 - 1973 SUBHRANSU K. RAY, M.D., Ph.D.

Internship: Beth Israel Medical Center, New York, NY 7/1973 - 6/1974 T. DANIEL TING, M.D., Ph.D.

TUSHAR M RANCHOD, M.D. Residency: Ophthalmology, State University of New York, Downstate

Medical Center, Brooklyn, NY 7/1974 - 6/1977 122 LA CASA VIA SUITE 223 WALNUT CREEK, CA 94598 Fellowship: Retina-Vitreous Fellowship (925) 943-6800 FAX (925) 943-6880

Manhattan Eye, Ear and Throat Hospital Cornell University Medical Center 20130 LAKE CHABOT ROAD SUITE 303 New York, NY 7/1977 - 6/1978 CASTRO VALLEY, CA 94546 (510) 733-1888 FAX (510) 881-5332 Board Certified: American Board of Ophthalmology 1979

491 30TH STREET Medical Licensure: New York, U.S. – 8/1972 California, U.S. – 6/1975 SUITE 102 OAKLAND, CA 94609 (510) 832-6554 Private Practice: Bay Area Retina Associates, California 1979 - Present FAX (510) 832-3119

Assistant Clinical Professor of Ophthalmology 1460 NO CAMINO ALTO SUITE 109 VALLEJO, CA 94589 University of California San Francisco Medical Center (707) 552-9596 San Francisco, CA 1980 - present FAX (707) 552-9599

Clinical Trials 2147 MOWRY AVENUE SUITE C-3 FREMONT, CA 94538 Principal Investigator – VAM Study, Verteporfin and Age Related Macular (510) 505-1430 FAX (510) 794-6264 Degeneration 1999 – 2000. Sponsor – Novartis, Inc. 2219 BUCHANAN ROAD SUITE 6 Principal Investigator – FOCUS Study for RhuFab V2 Phase II – 2002 ANTIOCH, CA 94509 (925) 522-8850 Sponsor – Genentech, Inc. FAX (925) 522-8851

15051 HESPERIAN BLVD. Principal Investigator – MARINA Study for RhuFab V2 Phase III -2003 SUITE D Sponsor – Genentech, Inc. SAN LEANDRO, CA 94578 (510) 317-1111 FAX (510) 317-1113 Principal Investigator – Ruboxistarin Study for Diabetic Macular Edema Phase III -2004 Sponsor –Eli Lilly, Inc. 5980 STONERIDGE DRIVE SUITE 117 PLEASANTON, CA 94588 Investigator – SCORE Study for BRVO/CRVO – 2004 (925) 463-8200 FAX: (925) 463-8201 Sponsor – NIH/NEI

Investigator – DRCR Studies for Diabetic Retinopathy – 2004 Sponsor – NIH/NEI

www.bayarearetina.com 13

Principal Investigator – HORIZON Study for RhuFab V2 Phase IIIb -2005 Sponsor – Genentech, Inc.

Principal Investigator – SAILOR Study for RhuFab V2 Phase IIIb -2005 Sponsor – Genentech, Inc.

Principal Investigator – ACU201-Cand5 Study Phase II -2005 Sponsor – Acuity Pharmaceuticals, Inc.

Investigator – PDEX Study-Combination Triple Therapy vs. Lucentis Monotherapy – 2006 Sponsor – Bay Area Retina Associates IST

Investigator – BRAVO Study for RhuFab V2 Phase III -2007 Sponsor – Genentech, Inc.

Investigator – CRUISE Study for RhuFab V2 Phase III -2007 Sponsor – Genentech, Inc.

Investigator – QUARK 003 Study for REDD14 siRNA Phase I -2007 Sponsor – Quark Pharmaceuticals, Inc.

Investigator – LUCEDEX Lucentis and Dexamethasone vs. Monotherapy Lucentis – 2008 Sponsor- Bay Area Retina Associates

Investigator- OASIS - Ocriplasmin for Treatment for Symptomatic Vitreomacular Adhesion Including Macular Hole- 2011 Sponsor-ThromboGenics

Investigator- SPECTRI - Lampalizumab Intravitreal Injections in Patients with Geographic Atrophy Secondary to Age-Related Macular Degeneration- 2014 Sponsor-Hoffmann-La Roche

Investigator- STOMP - Short-Term Oral Mifepristone for Central Serous Chorioretinopathy. A Placebo-controlled Dose Ranging Study of Mifepristone in the Treatment of CSC, IST- 2015 Sponsor: Roger Goldberg, M.D.

Investigator- VAPOR 1–DE-120 Injectable Solution for Age-related Macular Degeneration- 2015 Sponsor: Santen, Inc.

Investigator- AVENUE - RG7716 Administered Intravitreally in Patients with Choroidal Neovascularization Secondary to Age-Related Macular Degeneration- 2015 Sponsor: Hoffmann-La Roche

14 Investigator- BOULEVARD - RO6867461 in Participants with Center-Involving Diabetic Macular Edema (CI-DME) Phase II - 2016 Sponsor: Hoffmann-La Roche

Principal Investigator- PAVE - DE-122 Injectable Solution for the Treatment of Refractory Exudative Age-related Macular Degeneration Phase I/II- 2015 Sponsor: Santen, Inc.

Investigator- OMASPECT - Lampalizumab in Patients with Geographic Atrophy Secondary to Age-Related Macular Degeneration Who Have Completed a Roche- Sponsored Study – 2016 Sponsor: Hoffmann-La Roche, 2016

15 Attention Board of Optometry.

To whom it might concern,

Along with this letter you will find CV’s from all three doctors, CE applications, Summaries, Outlines, and

Presentation materials. I apologized for the information being a little late but one of the doctors was

Out of town and I didn’t get his presentation information until much later.

Let me know if you need any other information.

Hedy Rodriguez

Batra Vision Medical Group [email protected]

Uveitis

Following this lecture, attendees should be able to recognize the findings, categorize the types and understand how the most common causes of uveitis are currently managed.

17 Definition of Uveitis Overview Classification of Uveitis Granulomatous vs Non-granulomatous Unilateral vs Bilateral Symptoms Ocular findings Standardized Grading Scale for Anterior Chamber Inflammation

Examples of Anterior Uveitis • Traumatic iritis • HLA-B27 • Herpes simplex uveitis • Juvenile Idiopathic Arthritis

Examples of Intermediate Uveitis • Pars Planitis • Multiple Sclerosis • Endophthalmitis

Examples of Posterior Uveitis • Toxoplasmosis

Examples of Panuveitis • Sarcoidosis • Syphilis • Tuberculosis • Vogt-Koyanagi-Harada Disease

Herpes Retinitis • Acute Retinal Necrosis (ARN) • Progressive Outer Retinal Necrosis (PORN)

18 5/17/2017

Uveitis Uveitis: Inflammation of the Uvea Overview

.--~!..-. • 58/100,000 persons / c~.. ,.._., .-- ~. • Whites>non-whites • Genders equally affected (but women outlive men • Increasing prevalence with age Cr.ogJ. Leong, M.D. • Third learung cause of blindness in the dcvdoped countries Bay Area Retina Associates • 39% of chronic anterior uvcitis is truly J\fay 18, 2017 idiopathic

Classification of Uveitis Classification of Uveitis Classification of Uveitis

·D""• 111doctet11i.D c,~usD Intermediate Uveitis / Pars Planitis Anterior Uveitis • Pars Plana: "Snowbank" inflammatory cx:udatcs Posterior Uveitis • Iriti s: Inflammation of the iris • Vitreous: inflammatory cells and clumped \VBC's in the • Choroiditis: Inflammation primarily in the chocoid, • lridocyclicis: Inflammation of the iris and ciliary body vitreous e.g..• Punctate lnner Choroiditis (PIO

Classification of Uveitis Classification of Uveitis

Panuveitis Posterior Uveitis • Inflammation of all o f rhe layer.; of the uvea, e.g. Posterior Uveitis • Chorioretinitis: Inflammation o f the choroid> retina, uveitis secondary to tuberculosis, syphilis, sarcoidosis, e.g., Presumed Ocular Hiscoplasmosis Syndrome • Retinochoroiditis: Inflammation in the retina > Vogt Koyanagi Harada Disease, sympathetic (POHS) choroid, e.g, Toxoplasmosis retinochoroiditis ophthahrua

1 19 5/17/2017

Classification of Uveitis Classification of Uveitis Unilateral vs. Bilateral

Granulomatous • Thi.ck deposits of lymphocytes and cpithelioid cells on Non-granulomatous cornea1 endothelium • Fine deposits of lymphocytes on corneal endothelium • E tiology: Uveitis secondary to syphilis, sarcoidosis, Unilateral • Etiology: Uveitis secondary to Hl...... \.-B27, juvenile tuberculosis, to:xoplasmosis, Vogt Koyanagi Harada idiopathic arthritis, multiple sclerosis, inflammatory Disease, herpes zoster/simplex, sympad1etic • Etiology: Infectious, traumatic, post-operative, bowel disease, psoriasis, systemic lupus e ematosis o hthalmia idiopathic

Unilateral vs. Bilateral Uveitis Symptoms Ocular Findings

Bilateral Blurred vision and ocular pain • Inflammatory cells and flare (protein) in the aqueous • Etiology: Systemic infection, autoimmune, • Ocular redness / circum1imbal flush granu1omatous disease • Light sensitivity / photophobia • Keratic precipitates on corneal endothelium

Ocular Findings Ocular Findings Ocular Findings

• Hypopyon (layered \VBCs in inferior AC angle) Posterior synechiae (pupillary adhesions to lens) • Inflammatory glaucoma (inflammatory blockage of • Cataract (due to inflammation or steroid treatment) • Iris atrophy (secondary to chronic iritis) trabecular meshwock) • Vitritis: Vitreous inflammation • Iris nodules (WBCs on anterior iris stroma) • Inflammatory hypotony (ciliary body shutdown) • Pars plana "snowbank"' inflammatory (!}i.'Udates

2 20 5/17/2017

Standardized Grading Scale for Anterior Chamber Inflammation

$W;Cl;lr«UlfS~~lt.JU:m11," S-ftn#o1-lw....~W. ~ ~fl'u • <> 4:,. i.f

$,IJll".....s-... _.._""' :a,. ~ ..:llttlt J••. -~--_....,__...._.n • Chorioretinal inflammation • Optic disc hyperemia -~ • Retinal vasculitis • C staid macular edema

Anterior Uveitis: Human Leukocyte Anterior Uveitis: Human Leukocyte Anterior Uveitis: Traumatic Iritis Antigen HLA-B27 Uveitis Antigen HLA-B27 Uveitis - .~~;

• Etiology: accidental blunt trauma, fist 6ghts, sports injuries, car accidents • Associated diseases: Anlq•losing spondylitis. reactive • Diagnosis: ID..A-B27 blood test arthritis (Reiter syndrome). inflammatory bowel disease, • 20'%of icitis • Management Topical steroid and cydoplegic eyedrops, psoriatic acthritis • Findings: cells and flare, hyphema, subconjunctival periocular/intcavitreal steroid injections, NSAIDs, hemorrhage • Incidence: 40-70% of acute anterior uveitis systemic steroids. cyclosporine, metlmtrexate, • i\fanagement cycloplegic and steroid eyedrops • Findings: AC fibrin, hypopyon, posterior synediiae azathiopcine, etaneccept (Enbrel)

Anterior Uveitis: Herpes Simplex Anterior Uveitis: Herpes Simplex Anterior Uveitis: Juvenile Idiopathic Keratouveitis Keratouveitis Arthritis

• Clinical diagnosis: unilateral anterior uveitis with high IOP Etiology probable autoimmune reaction to ocular antigens Etiology: Herpes simple.._ vims Laboratory diagnosis:a Negative HSV titer mJes out HSV; with a possible genetic predisposition • • Incidence: 9'% of anterior uveitis PCR testing for: HSV DNA in the aqueous Incidence: 6% of uvcitis arc in children of which the most fre9~ent cause is JIA. 10~20% of JlA patient will de\·clop • Findings: 85% anterior>15% posterior uveitis, • Management cycloplegic and steroid eyedrops, treat uveltls decreased corneal sensitivity, iris atrophy, kecatic glaucoma, oral antiviral medications (Acyclovir, valacyclovir, • Findin_gs: AC cells with white eye, keratic precipitates, precipi~tes, posterior synechiae, glaucoma famciclovir) postenor sp1echiae, band kecatopatby. cata.J::act, CME

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Anterior Uveitis: Juvenile Idiopathic Intermediate Uveitis: Pars planitis Intermediate Uveitis: Pars planitis Arthritis . •c,

./ • Diagnosis: Clinical presentation; no specific testing • Etiolom,>: Autoimmune available Diagnosis: ANA is positive in 80%, HLA-DR5 • Incidence: 10% of uveitis is due to pars planitis • Management: Periocular steroid injections,, cryopexy of • Management: Steroid and cycloplegic cyedrops, of NSAIDs, systemic steroids, methotrexate, etanercept • Findings: Vitreous cells, pacs plana "snowbank" pars plana, vitrectomy+cndolascr, treatment inflammatory glaucoma, cyclosporine, azathioprine, (Enbrel), infliximab (Remicade), adalimumab (Humira), exudates, retinal v::i.sculitis, CME, cataract, inflammatory mcthotrexate, cyclophosphamide abatacept {Orencia), tocilizumab (Actemra) glaucoma

Intermediate Uveitis: Multiple Sclerosis Intermediate Uveitis: Post-operative Endophthalmitis

• Etiology: Multiple sclerosis • Presentation: 3-14 days post-op, progressively worsens osis: I-ILA-DR2 antigen, brain j\.fRJ scan • Incidence: 14% of uveitis patients have MS, 27% of • Diagn • Symptoms: Blurred vision, redness, pain i\{S patients have uveitis • Afanagcmcnt Peciocular steroid injections, treatment of • lncidence: 0.08-0.68% after cataract surgery-, 0.2-0.4% glaucoma, cyclospocine, azathioprine, Findings: Retinal "\"'aSculicis, CME, vitreous cells, in£lammatory after secondary IOI.., 0.2-9.6% after glaucoma filter, otrexate, cyclophosphamide retmbulbar neuritis meth 0.03-0.05% after vitrectomy

Intermediate Uveitis: Post-operative Intermediate Uveitis: Endogenous Intermediate Uveitis: Endogenous Endophthalmitis Endophthalmitis Endophthalmitis

-.... Findings: corneal edema, AC cells and fibrin, hypopyon, vitritis, retinal vasculitis and infectious retinitis • Endogenous: infection that sp reads from body to eye • Findings: Infectious retinitis, vitritis • Diagnosis: Culture blood, vitreous and any indwelling for • Associated conditions: diabetes,J-1IV,1V drug abuse, • Management: Sample the aqueous / vitreous cad1eter for bacteria and fungus culture+sensitivity of organisms, intravitceal injection immunosuppressive therapy, indwelling catheter, recent • 1ianagcmcnt: Initiate treatment \\-1th intravenous intravenous infusion of vancomycin and cefuzidime, vitrectomy with vaocomycin and cefta.zidime, revise antibiotics depending intravitreal antibiotics if Va is only LP • Incidence: 2-8% of endophthalmitis cases u culture rcsu1ts

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Posterior Uveitis: Toxoplasmosis Posterior Uveitis: Toxoplasmosis Posterior Uveitis: Toxoplasmosis

• Congenital: passed from m othct to ferus in utero with • Diagnosis: Toxoplasma Igi\f and IgG titers,, PCR of later reactivation o f scar aqueous and vitreous Etiology: Toxoplasma gondi.i, a parasite carried by cats. • Acquired: primarily in immunocompromised patients • Treatment: Pyrimeth.'llllllle, sulfadiazine and oral Intermediate hosts are humans, mammals, birds and • Ocular findings: Active retinochoroiditis and vitritis steroids. Alternative treatment regimens include reptiles. i\fost common cause of infectious posterior adjacent to a congenital scar; large, confluent and systemic / intravitreal dindamycin, oral Bactrim, uveitis bilateral lesions in immunocompromised patients.. azithromycin, atovaquone, intravitreal dexamethasone

Panuveitis: Sarcoidosis Panuveitis: Sarcoidosis Panuveitis: Sarcoidosis

• Etiology: Unknown. Possible genetic and • Systemic findings: no n-caseating granulomas, environmental factors. Possible association with HJ..A. • Ocular findings: conjunctiva.I, scleral and lacrima1 gland pulmonary hilar adenopath y, crythema nodosum, DRBl antigen and exposure to tuberculosis. granulomas, granulomatous anterior uveicis, iris lymphadenopathy, arthritis, cough and polymyositis • Incidence: 3-10% of all uveitis. African Americans> nodules, posterio r synechiae, cataract, vitritis, • Diagnosis: serum angiotensin converting enzyme whi tes, females>males choroiditis, retinal vasculitis (candJe-\vax drippings), (ACE) and serum lysozyme, chest X-CIJ~ chest CT scan, • S toms: blurred vision, redness, floaters, e e ai n Q\.ffi,, optic neuropathy and inflammatory glaucoma conjunctiva! biopsy, whole body gallium scan

Panuveitis: Sarcoidosis Panuveitis: Syphilis ,IJ __. ... ,____...... ,.,,._*··...., : =--..-?'_.;.._,.:_-:::_:_.~~-~·~-::

• Ocular findings: Jridocyclitis, iris nodules, keratic • E tiology: SID infection by Trepo nema Pallidurn; precipitates, ,.,;tritis, multi.focal chorioreriniris, retinal Acquired >>Congenital cases v.isculitis, CME, optic neuropathy, Argyll Robertson • Treatment Topical steroid and cycloplegic eyedrops, • Incidence; <5% o f all uveitis cases~ high risk sex is the pupil, inflammatory glaucoma oral steroids, peciocular steroid injections, methotrexatc, key facto r, 67% of acquired cases occur in men who • Systemic findings: Genital diancres,. skin rash, unpaired q,closporine, inflixirnab (Remicade) have sex with men; high rate of mv coinfection balance, deafuess, dementia, aortic aneurysm

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Panuveitis: Tuberculosis Panuveitis: Tuberculosis

• Etiology: Mycobacteriwn rubcrcu1osis, an airborne • Incidence: 3 cases/100,000 people in USA; 1-2% of all • Diagnosis: RPR (Nonspecific) and FTA.ABS (specific), pathogen with primacy pulmonary involvement cases of uveitis; higher risk in immunocompromised lumbar puncture for CSF cells, protein and VDRL • Ocular findings: granulomatous panuveicis, vitriris, patients, health oue workers and immigrants from serology choroidicis, vasculitis, CME and optic neuropathy endemic countries • Treatment Topical steroid and cycloplegiceyedrops Systemic findings: Secondary involvement of the bones, • Diagnosis: PPD skin test, quantiferon gold blood test, culture, PCR of aqueous/vitreous • Ncuro hilis: Intravenous Penicillin G x 14 da s brain, liver, kidne sand heart chest X·ray, sputum

Panuveitis: Vogt Koyanagi Harada Panuveitis: Vogt Koyanagi Harada Panuveitis: Tuberculosis Disease Disease . . , ' ,' .,~/ \

" M \. If. ,;,

C • • ,:; j (y • -;-0;r .~ - .,. Treatment • Ocular F'mdings: Choroid.iris with mu1tifocal serous • Etiology: Unknown but assumed to be autoimmune • Systemic tubcrrulosis is treated with rif.unpin, isoniazid, retinal detachments,. optic disc hyperemia, enthambutol, and pyrazinamide • Incidence: 1-3% of uveitis in USA; 7.9% of uveitis in granulomatous panuveitis, choroidal depigmencation Japan; darker pigmented individuals; women>men • Ocular manifestations arc treated with topical steroid • Systemic Findings: Poliosis (loss of melanin in hair), and cycloplegic eyedrops in conjunction with systemic • Symptoms: Headache. photophobia. blurred vision, vitiligo (loss of melanin in skin), alopecia (loss of hair), antibiotics nausea. eye pain tinnitus (ringing in ears), dysacusis (loss of hearing)

Panuveitis: Vogt Koyanagi Harada Ocular Complications of HN Ocular Complications of HIV Disease

• Etiology: HIV incidence (37,600 new cases/year in 2014) declining due to HAART (highly active anti Diagnosis: Fluorescein and ICG angiography, OCT retroVlral therapy. Ocular complications occur in 70 scan, fundus hyperautofluorescence; lumbar puncture 80% HIV patients; increased risk when CD4 count shows CSF plcocytosis (increased WBC's and protein) drops to < 200 cells/cubic mm • Treatment Systemic corticosteroids, methotrexate, • Ocuhr Findings: Kaposi's sarcoma, molluscum • Ocular Findings: Herpes zostcr ophthalmicus, herpes azathioprine, cyclosporine concagiosum keratitis

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Ocular Complications of HN Ocular Complications of HIV Ocular Complications of HN

Ocular Findings: HIV retinopathy, ocular syphilis, • Ocular Findings: Frosted branch angiitis, tox:oplasmosis retinochoroiditi.s, ocular lymphoma, • Ocular Findings; fungal endophthalmiris cytomegalovirus (CMV) retinitis

Panuveitis: ARN vs. PORN Panuveitis: ARN vs. PORN Panuveitis: ARN vs. PORN

• ARN: Acute Retinal Necrosis (not • Symptoms: Blurred vision, vitreous floaters, • Medical therapy: Intravenous acyclovir x 14 days immunocompromised) photophobia initially in one eye followed by oral valacyclovir x 3 months or longer • PO.RJ"l: Progressive Outer Retinal Necrosis • Ocular Findings: Rapidly progressive pecipheral retinal • Surgical Therapy: Prophylactic laser photocoogufation (ill1Il1llllocompromised or HIV) necrosis with severe panuveitis and occlusive retinal of l:uge retinal breaks if retina not detached. Etiology: Herpes (zoster or simplex) retinitis in both vasculitis, retinal detachment, optic atrophy Vitreccomy with endolaser and silicone oil ramponade conditio ns • Dia osis: PCR of intraocular fluid s for he cs DNA if retina is detached.

Panuveitis: ARN vs. PORN The Final Word

• History, history, history: Most cases of uveitis have a cause and the patient's medical history will give you the clues to finding it. • Always dilate and examine both eyes: Anterior segment inflammation often has a posterior component that will indicate t!1e cause. • Be wary of simply treating with topical steroids without Medical therapy: Intravenous acyclovir x 14 days determining the cause of the uveitis: steroids suppress oral x 3 months or longer foUowed by valacyclovir inflammation, delay making a diagnosis and, in some Surgical Therapy: Prophylactic laser photocoogulation cases, can allow the underlying condition to worsen. of large retinal breaks if retina not detached. Vi tree tomy with endolaser and silicone oil tamponade Thawyow if retina is detached.

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BayAreaRetinaAssociates M E D I C A L G R O U P Craig J. Leong, M.D. CURRICULUM VITAE

Internship: Beth Israel Medical Center, New York, NY 7/1973 - 6/1974 T. DANIEL TING, M.D., Ph.D.

TUSHAR M RANCHOD, M.D. Residency: Ophthalmology, State University of New York, Downstate

Medical Center, Brooklyn, NY 7/1974 - 6/1977 122 LA CASA VIA SUITE 223 WALNUT CREEK, CA 94598 Fellowship: Retina-Vitreous Fellowship (925) 943-6800 FAX (925) 943-6880

Investigator – DRCR Studies for Diabetic Retinopathy – 2004 Sponsor – NIH/NEI

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