WAEPS Medical Personnel Conference March 20, Deanne M. Nakamoto, MD Achieve Eye and Laser Specialists Silverdale, WA

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1 WAEPS Medical Personnel Conference March 20, 2015 Deanne M. Nakamoto, MD Achieve Eye and Laser Specialists Silverdale, WA

2 Up to half of UVEITIS pa/ents have GLAUCOMA.

3 What is uvei/s?

4 Why should we care? 40,000 new cases a year in US 10% of legal blindness in the US Uveitis causes significant vision loss from cataracts, glaucoma, and macular edema. In about half of patients, uveitis will be a part of a systemic disease that is associated with significant morbidity and mortality. Up to half of uveitis patients have glaucoma.

5 Causes of Uvei/s AUTOIMMUNE INFECTIOUS HSV/VZV/CMV Toxoplasmosis Syphilis Lyme TB Fungi more Idiopathic Rheumatoid arthritis Sarcoidosis HLA B27 (AS, Reiter, UC) Juvenile Idiopathic Arthritis Wegener s granulomatosis Posner-Sclossman more MASQUERADE Ocular Ischemic Leukemia Lymphoma Metastatic CA Immune recovery more

6 Symptoms of Uvei/s Pain Photophobia Red eye Decreased vision Floaters Note: Kids with JIA are usually asymptomatic! 6

7 What is seen at the slit lamp AC cells drsobol.com

8 AC flare

9 Kera/c precipitates (collec/ons of macrophages on endothelium of cornea)

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12 Iris Nodules

13 Posterior synechiae revophth.com

14 Peripheral Anterior Synechiae

15 Vitreous cell

16 Posterior uvei/s

17 How do uvei/s pa/ents lose vision over /me? 1. Cataract 2. Glaucoma 3. Macular edema

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19 Uveitic Glaucoma Angle changes Aqueous composition Trabeculitis Steroid-response POAG

20 Specific inflammatory diseases that cause high IOP with inflamma/on INFECTIOUS Herpes virus (HSV, VZV, CMV) (30%) Toxoplasmosis (10-40%) Sarcoidosis (10%) Glaucomatocyclitic crisis (Posner- Schlossman) Syphilis (20%) NONINFECTIOUS Schwartz- Matsuo syndrome Microhyphema Lens- induced uveitis Angle closure with secondary iritis

21 Herpes Simplex and Zoster Iri/s mrcophth.com oculist.net emedicine.medscape.com

22 Herpes Zoster Ophthalmicus Cutaneous Herpes Simplex

23 Stellate KP Emedicine.webscape.com

24 Toxoplasmosis

25 Sarcoidosis

26 Cor/costeroid induced glaucoma One- third of the general population will get elevated IOPs from topical corticosteroids in the first two weeks. (Becker 1965) Another 1/3 will develop it at some point months to years later. 90% of POAG patients will have at least a 6mm increase in IOP after 1 month of topical dexamethasone (Weinreb 1985) About 40-51% with Retiserts will get IOPs above 30. (Goldstein 2007) 6% needed glaucoma surgery within 34 weeks (Jaffe 2006) and 36.6% needed IOP surgery within 3 years (Goldstein) In general, corticosteroid- response glaucoma is more easily controlled- - less drops and less filtration surgery than non- corticosteroid response glaucoma patients. (Sallam 2009)

27 Treatment of Uvei/c Glaucoma STEP 1. Control inflamma/on. STEP 2. Treat the glaucoma. IN THIS ORDER (OR CONCURRENTLY)

28 STEP ONE: Controlling the Inflamma/on

29 If there is a specific cause, treat that cause. HSV/VZV iritis à Valacyclovir or acyclovir + steroids CMV à gancyclovir or valgancyclovir Toxoplasmosis à Bactrim, Clindamycin, sulfadiazine, pyrimethamine Sarcoidosis à Steroids, immunosuppression

30 Treatment of Uvei/s 1. Immediate control - Corticosteroids 2. Long term control - Immunomodulatory agents - Corticosteroid implants CAN PREVENT UVEITIS FIRES 3. Visual rehabilitation - Surgery to clear media (cataract, vitrectomy, K transplants)

31 Topical Cor/costeroids Prednisolone 1% or Dexamethasone These agents get as far as the iris. They have no effect on anything more posterior to that. Started hourly while awake for active uveitis. Immediate Control

32 Topical Cor/costeroids Durezol (difluprednate) About 6x stronger than prednisolone (equal in efficacy to betamethasone). Steroid-response IOP elevation tends to be higher and more frequent. Immediate Control

33 Periocular and Intravitreal Cor/costeroids Injections periocular or intravitreal dexamethasone or triamcinolone (Triescence) These have posterior eye efficacy. These typically last two-six months. cms.revoptom.com Immediate Control myvisiontest.com

34 34 Steroid implants: Ozurdex Dexamethasone Non-infectious uveitis Can be done in office Effect up to 6 months Long term Control

35 Re/sert Implant Severe non-infectious posterior uveitis Fluocinolone acetonide 0.59 mg Lasts about 2 years 90% need cataract extraction, 30% need glaucoma surgery. 35

36 Oral cor/costeroids: Prednisone (1mg/kg)

37 The problem with cor/costeroids. Side effects: Increased IOP and Cataract Oral: weight gain, suppressed immune system, bone loss, skin changes, mood swings, insomnia Relying on PRN immediate control options leaves you with synechiae & macular scarring over the long run = cumulative VISION LOSS. SEVERITY OF INFLAMMMATION Synechiae, macular scarring TIME

38 Indica/ons for immunosuppression Corticosteroid intolerance (steroid response glaucoma, cataract) Multiorgan system disease (i.e. joint + eye) Repeated episodes (>3) with macular edema (potentially permanent damage of recurrent flares) about 40 drop-months (qid x 10 months) If you can t taper Prednisone to <10mg after 3 mo Absolute indications: Certain serious uveitis (Behcet s, VKH, SO, rheumatoid scleritis) Contraindications: unreliable patient/poor followup, family history of cancer, latent infectious disease/ HIV, Long term Control

39 Long term Control Uvei/s toolkit Cytoxan Alkylating agents Infliximab (Remicade) Adalimumab (Humira) Abatacept (Orencia) IVIg BIOLOGICS (ANTI-TNF) CsA Methotrexate Mycophenolate mofetil (CellCept) ANTIMETABOLITES Azathioprine (Imuran)

40 STEP TWO: Treat the Glaucoma

41 Medical therapy of glaucoma Same medical treatment: prostaglandins, betablockers, alpha agonists, and carbonic anhydrase inhibitors. Prostaglandins are not contraindicated, but often used as a second line agent. They do not exacerbate inflammation. The link between prostaglandins and exacerbation of uveitis is only anecdotal In a study of 246 uveitic eyes, no difference in inflammation seen was seen between groups that were treated with prostaglandins and those treated with other glaucoma medications. (Sallam 2009)

42 Surgery: General principles If at all possible, you need three months of inflammatory control. (With or without medications) Cases in which you don t have the luxury of inflammatory control: STEROIDS! Avoid anterior segment lasers in general. Avoid cyclodestructive procedures in general.

43 Preopera/ve steroids Subtenon s injection of triamcinolone within a month prior to procedure (give inferiorly for most glaucoma procedures) Preoperative oral corticosteroids Perioperative pulse intravenous corticosteroids 1 gram solumedrol IV to induce lymphocyte lysis Topical corticosteroids alone may or may not be enough.

44 Filtering surgery with MMC or tube shunts About 20% greater chance of failing vs nonuveitic eyes Can do Trabeculetomy if Not children/young adult and not likely to scar Have excellent control over inflammation on immumosuppresion or Retiserts (long term control) Require very low IOP afterward Tube shunts Place posteriorly for severe uveitis (with tube just behind IOL) to minimize tube- iris and tube- cornea touch, to reduce iritis) If patient does not have cataract can place tube anteriorly and plan to move tube posteriorly at later date if need be.

45 Minimally invasive approaches SLT Trabectome istent

46 A hypothe/cal pa/ent.

47 CC/HPI Red? Pain? Photophobia? Vision? Floaters? 47

48 HPI con/nued When did the symptoms start? If episodic, when was the first episode, how often are episodes, and how long between episodes? Do their pressures go up only with steroid treatment? Past Therapies: Surgeries? Drops? Oral steroids? Injections?

49 More history taking Medications/Current therapy: All drops and systemic medications as they relate to glaucoma or uveitis. This may include intramuscular and intravenous drugs, immunosuppressive drugs. Past Medical History: RA? JIA? Lupus? Sarcoidosis? MS? Social history: Smoking? Drinking? Travel? Cats? Tattoos? Family History: FH glaucoma? Autoimmune disease?

50 High Yield Uvei/s ROS Joint/back pain à JIA, RA, HLAB27, Lupus Rashes à Syphilis, Lyme, Behcet, sarcoidosis Mouth sores à HSV, Behcet s, Lupus, IBD SOB, Cough à Sarcoidosis, Wegeners, TB Constipation/Diarrhea à Ulcerative colitis

51 Summary and Take Home Points Infection is a common reason for high IOPs in the presence of acute inflammation. There are many reasons for uveitic patients to get glaucoma in the long run. Prostaglandins are OK in uveitis patients. Inflammatory control is everything. The number one mistake is tolerating inflammation because of fear of steroid- response or cataract. The number two mistake I see is tolerating IOP spikes and letting the nerve die because of treating uveitis flares with steroids. i.e. immunosuppression! Before we operate, preoperative inflammatory control for three months.

52 References Becker B. (1965) Intraocular pressure response to topical corticosteroids. Invest Ophthalmol 4: Chang JH, McCluskey P, Missotten T, Ferrante P, Jalaludin B, Lightman S. (2008) Use of ocular hypotensive prostaglandin analogues in patients with uveitis: does their use increase anterior uveitis and cystoids macular oedema? BJO 92: Heinz C, Koch JM, Zurek- Imhoff B, Heiligenhaus A (2009) Prevalence of Uveitis Secondary Glaucoma and Success of Nonsurgical Treatment in adults and chilren in a tertiary referral center. Ocular Immunology and Inflammation 17: Jaffe GJ, Martin D, Callanan D, Pearson PA, Levy BL, Comstock T. Fluocinolone acetonide implant (Retisert) for Noninfectious Posterior Uveitis: Thirty- Four Week Results of a Multicenter Randomized Clinical Study. (2006) Ophthalmology 113: Goldstein DA, Godfrey DG, Hall A, et al. Intraocular pressure in patients with uveitis treated with fluocinolone acetonide implants. Arch Ophthalmol 125: Korenfeld MS, Silverstein SM, Cooke DL, Vogel R, Crockett RS, (2009) Difluprednate Ophthalmic Emulsion 0.05% (Durezol) Study Group. Difluprednate ophthalmic emulsion 0.05% for postoperative inflammation and pain. Journal of Cataract & Refractive Surgery. 35 (1) Noble J, Derzko- Dzulynky L, Robinovich T, Birt C. (2006) Outcome of trabeculectomy with intraoperative mitomycin C for uveitic glaucoma. Can J Ophthalmology 42: 89-94, Panek WC, Holland GN, Lee DA Christensen RE. (1990) Glaucoma in patients with uveitis. Br J Ophthalmol 74: