KU EYE Optomcon

KU EYE OptomCon

CE Optometry Conference Friday, September 30, 2016 1:00 pm - 5:00 pm

SPONSORED BY THE Department of Ophthalmology University of Kansas Medical Center

PROGRAM AGENDA

1:00 – 2:00 p.m. Update on Pseudotumor Cerebri Syndrome – Thomas J. Whittaker, JD, MD, Professor, Department of Ophthalmology, University of Kansas Medical Center

2:00 – 4:00 p.m. Anterior Uveitis: Common Infectious and Non- Infections Etiologies – Dominick Opitz, O.D., F.A.A.O., Illinois College of Optometry, Chicago, IL

4:00 – 5:00 p.m. Detecting Functional Change in Progressing Glaucoma – Paul Munden, MD, Associate Professor, Department of Ophthalmology, University of Kansas Medical Center

Financial Disclaimer

• I have no financial interest in any matter Update on Pseudotumor Cerebri discussed in this presentation. Syndrome

Thomas J. Whittaker MS JD MD

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 for cases with • Initial results of IIHTT—Idiopathic Intracranial papilledema Hypertension Treatment Trial – New criteria for cases without papilledema • – Diet and Diamox vs Diet and Placebo in treatment New terminology: no longer benign idiopathic 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).

Classification: Secondary PTC

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 Revised Diagnosis Criteria Without Papilledema Revised Criteria for Diagnosis A. Papilledema In the absence of papilledema, a diagnosis of pseudotumor cerebri syndrome B. Normal neurologic examination except for cranial nerve abnormalities can be made if: C. Neuroimaging: Normal brain parenchyma without evidence of 1. B–E from above are satisfied, and hydrocephalus, mass, or structural lesion and no abnormal meningeal 2. In addition the patient has a unilateral or bilateral abducens nerve enhancement on MRI, with and without gadolinium, for typical patients palsy (female and obese), and MRI, with and without gadolinium, and In the absence of papilledema or sixth nerve palsy, a diagnosis of magnetic resonance venography for others; if MRI is unavailable or pseudotumor 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 diagnosis of pseudotumor cerebri syndrome is definite if the patient fulfills criteria A–E. The diagnosis is considered probable if criteria A–D are met but the tortuous optic nerve measured CSF pressure is lower than specified for a definite diagnosis. – iv. Transverse venous sinus stenosis

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

9/26/2016

Disclosures Anterior Uveitis: Common Infectious and Non- •Shire • B+L (Valeant) Infections Etiologies • Allergan Dominick L. Opitz, O.D., F.A.A.O. • Glaukos Associate Professor of Optometry Senior Director, Ophthalmology Services and Practice Development Illinois College of Optometry

Outline

• Classification – Anatomy – Clinical course – Histopathology – Etiology • Specific Conditions – Non-infectious CASES – Infectious – Other

Clinical Approach to Uveitis

History (symptoms)

Physical exam (signs)

Anatomical classification

Associated factors

Lab studies CLASSIFICATION OF UVEITIS

Etiology

Treatment 14

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Summary Anatomical Classification Based on… Classification • Anatomy • anterior uveitis (iritis, iridocyclitis, and • what part of the uveal tract is affected • Clinical Course anterior cyclitis) •Acute • intermediate uveitis (para planitis, • Chronic • Recurrent posterior cyclitis, and hyalitis) • Histopathology • posterior uveitis (focal, multifocal, or • Granulomatous diffuse choroiditis, chorioretinitis, retinitis, • Nongranulomatous • Etiology and neuroretinitis) • Infectious • panuveitis (anterior chamber, vitreous, • Noninfectious • Masquerades retina, and choroid)

2 Sub-classes of Anterior Uveitis: Why Localize the Differ in Histopathophysiology Inflammatory Process? Granulomatous Non-granulomatous • The anatomical location of the • May result from an • Inflammation of the iris and autoimmune reaction or the ciliary body causes a inflammatory process is one of the most breakdown of the blood important clues to pathogenesis and from the host's immune ocular barrier. response to a systemic • This condition allows both treatment infectious process protein and WBCs to – Syphilis extravagate into the – Lyme disease aqueous, resulting in the • Anterior typical iritis signs of cell and – tuberculosis (TB) flare. • Intermediate – local reactivation of • Typically, but not always, herpetic viral infection. • Posterior non-infectious • Panuveitis

Granulomatous Inflammation Clinical Course of the Uveitis

• An inflammatory manifestation of infectious, toxic, • Acute describes the course of specific uveitic allergic, autoimmune and neoplastic origin. syndromes characterized by sudden onset and • Characterized by inflammatory cells of the limited duration mononuclear phagoctye system that take the form – Lasts <3 months of: • Chronic describes persistent duration with 1. Macrophages relapse <3 month after discontinuation of 2. Epithelial cells therapy. 3. Multinucleated giant cells – Last >3months • Recurrent describes repeated acute episodes • Can be an indicator of Chronic Inflammation too! separated by periods of inactivity without treatment > 3 months in duration.

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Onset Duration

• The onset described as sudden or • The duration of an attack of uveitis: insidious based on history. – Limited • < 3 months in duration – Sudden – Persistent • Symptoms and clinical signs “suddenly” appear • > 3 months in duration. – Insidious • Slow gradual development of symptoms, signs • Sometimes patients are only mildly symptomatic

International Uveitis Study Group (IUSG) in 2009 • Designed a simplified, clinical classification system for uveitis based on etiological criteria.

• 3 main categories: – infectious (eg, bacterial, viral, fungal, parasitic) – noninfectious (eg, known systemic associations, no known systemic associations) – masquerade (eg, neoplastic, non-neoplastic).

What Causes Uveitis? Assessment vs Impression

Based on the International Uveitis Study • Assessment: Group (IUSG) Clinical Classification of Uveitis – anterior uveitis • Non-infectious • Impression: • Infectious – Bacterial – Acute vs Chronic vs Recurrent –Viral – Fungal – Unilateral vs bilateral – Parasitic – Others – Granulomatous vs non-granulomatous • Masquerade (Neoplasmic vs. Non-neoplasmic) – Infectious vs non-infectious vs masquerade – Intraocular cells not due to immune mediated uveitis

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Clinical Approach to Uveitis

History (symptoms) Physical exam (signs) Underlying Causes of Anatomical classification Anterior Uveitis

Associated factors

Lab studies

Etiology

Treatment 40

Non-Infectious Etiologies Presentation Points Acute Chronic HLA-B27 Auto-immune Diseases • The condition •Ankylosing Spondylitis •Lupus • Signs, symptoms, etiology •Reiter’s •Wegener’s • The type of uveitis •Inflammatory Bowel (Colitis, Crohn) •Polychrondritis • Acute, chronic, recurrent •Psoriatic Arthritis • Granulomatous vs non-gran Tubulointerstitial Nephritis Fuch’s Heterochromia • The typical work-up Glaucomatocyclitis Crisis Idiopathic • Labs Lens associated (phacolytic) Behcet’s • Referrals Trauma and post-operative Sarcoidosis • Who to best manage the systemic disease Drug induced (Ribabutrin, Cidfovir) Juvenile Rheumatoid Arthritis (JRA) • Treatment Juvenile Idiopathic Arthritis (JIA) •Systemic Behcet’s Vogt-Koyanagi Harada Disease (VKH) • Ocular Sarcoid Sympathetic Ophthalmia Idiopathic 44

Infectious Uveitis Masquerades Bacterial Viral Fungal Parasitic Other Syphilis Herpes Simplex Histoplasmosis Toxoplasmosis Non-Neoplasmic Neoplastic virus (HSV) Retinitis Pigmentosa (RP) CNS Lymphomas Tuberculosis Varacella-zoster Candidiasis Toxocariasis virus (HZV) Non-Hodgkin Lymphoma Lyme Disease Cytomegalovirus Aspergilliosis Cysticercosis Ocular Ischemic Syndrome Hodgkin Lymphoma (CMV) Endophthalmitis Epstein-Barr Cryptococcosis Diffuse unilateral virus (EBV) subacute Chronic retinal detachment Leukemia neuretinitis (DUSN) Intraocular FB Uveal Melanoma Leptospirosis Rubella coccidioidomycosis Onchocerciasis Ocular West Nile Virus nocardiosis (WNV) Pigment dispersion syndrome Retinoblastoma Bartonella Adenovirus (PDS) henselae Juvenile xanthogranuloma Mononucleosis Influenza Metastatic Tumors 45 46

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Non-Infectious Etiologies Acute Chronic HLA-B27 Auto-immune Diseases •Ankylosing Spondylitis •Lupus •Reiter’s •Wegener’s •Inflammatory Bowel (Colitis, Crohn) •Polychrondritis •Psoriatic Arthritis Tubulointerstitial Nephritis Fuch’s Heterochromia Glaucomatocyclitis Crisis Idiopathic Lens associated (phacolytic) Behcet’s Trauma and post-operative Sarcoidosis NON-INFECTIOUS Drug induced (Ribabutrin, Cidfovir) Juvenile Rheumatoid Arthritis (JRA) Juvenile Idiopathic Arthritis (JIA) ETIOLOGIES Behcet’s Vogt-Koyanagi Harada Disease (VKH) Sarcoid Sympathetic Ophthalmia Idiopathic 47 48

Most Common Non-Infectious HLA-B27 Underlying Etiology for AU • Human cells and tissues contain surface markers that enable the body to differentiate its own cells from foreign material. • 50% of acute anterior uveitis (AAU) test +HLA-B27 • Genotype located on the short arm of Chromosome 6. • AND 50% of HLA-B27+ AAU will go on to develop one of the • HLA-B27+ patients have a protein found on white blood seronegative arthritis cells that stimulate an immune reaction to self. – CRAP • Chron’s/Inflammatory Bowel diseases • Present in 1.4-8.0% of population • Reiter’s Syndrome (Reactive Arthritis) • 50-60% of acute or recurrent anterior uveitis, may be • Ankylosing Spondylitis HLA-B27 positive. • Psoriatic Arthritis • Non-granulomatous • 25% who have been dx with HLA-B27 arthritis will develop AAU • Several autoimmune diseases collectively called • Up to 70% of Caucasian pts with AAU are HLA-B27 seronegative spondylarthropathies(-RF) positive. • are strongly associated with both acute uveitis and +HLA-B27. • 1st attack 20-40 yrs of age • 10% suffer severe visual impairment or blindness – Most commonly due to CME

Typical Penotype of Seronegative HLA-B27-positive AAU Spondyloarthropathies • Sudden onset (Acute) • Unilateral • Ankylosing Spondylitis – Often alternating – Rarely bilateral • Reiter’s Syndrome (Reactive Arthritis) • Reiter’s the exception • Non-granulomatous AAU • Chron’s/Inflammatory Bowel diseases • More likely to have: –fibrin • Psoriatic Arthritis – hypopyon – Posterior Synechia • High tendency for recurrences • Significant association with other HLA-B27-related systemic diseases. • Males more than females

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Seronegative Seronegative Spondyloarthropathies Spondyloarthropathies • Chron’s/Inflammatory Bowel diseases • Group of disorders that share many • Reiter’s Syndrome (Reactive Arthritis) clinical, pathological and immunogenic • Ankylosing Spondylitis features – Radiographic sacroiliitis with or without • Psoriatic Arthritis accompanying spondylitis – Inflammatory asymmetric peripheral arthritis predominantly of lower limbs – RF and ANA negative – HLA-B27 likely positive 53

Ankylosing Apondylitis (AS) Ankylosing Spondylitis

• Inflammatory arthropathy most frequently seen in males.

• Early symptoms include lower back pain and stiffness after inactivity (ie: sleeping) that can progress to severe deformity of the lower back

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• SI x-rays may show sclerosis and narrowing of the joint space • Inflammation of the sacroiliac joints is the classic sign – the spinal column is www.med.mun.ca also frequently involved.

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The AS Stereotype? What to do if You Suspect AS? • Onset in young 20-30 yo • 1% of population • Labs: • More in Caucasians • HLA-B27 • ESR • Male (4:1) – But non-specific • Acute non- • Imaging: granulomatous Anterior • X-rays of the SI joints (poor imaging, but the uveitis standard) • Lower back pain that • CT or MRI of the SI joints (better, but more costly) improves with • Referral: movement/exercise • Rheumatologist

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Reiter’s Syndrome Infection and HLA-B27 Reactive Arthritis • Non-infectious immune-mediated • Classic diagnostic triad: inflammation 1. Arthritis-98% – Occurs after infections of the genitourinary 2. Urethritis -74% 3. Conjunctivitis-58% or gastrointestinal tract. – Reiter’s/Reactive Arthritis • Anterior Uveitis in 3-12% – Chron’s • Etiology is thought to result from infection from Chlamydia, • Bacteria thought to be responsible: Ureaplasma urealyticum, Shagella, Salmonella, and Yersinia. • Salmonella, Shigella, Campylobacter, – Arthritis begins within 30 days of infections? Klebsiella, and Yersinia, or Chlamydia • Knees, ankles, feet, wrists trachomatis,

How Does Bacteria Cause a Non-Infectious AAU? Other findings

• “uveitogenic” peptides from certain • Keratoderma bacteria are bound and presented by HLA- blennorrhagicum B27 to T cells. • Circinate balanitis • These microbe-derived antigens may trigger CD8+ T-cell immune responses • Plantar fasciitis that cross-react with self-tissue antigens • Achilles tendonitis (molecular mimicry) • Sacroiliitis • uniquely found in the uvea or joint tissue, • Nailbed pitting resulting in autoimmune tissue • Palate ulcers inflammation. • Tongue ulcers

Cheng J., et al. Surv Ophthalmol. 2005; 50(4): 364–388 64

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What to Do if You Suspect Reiter’s/Reactive Uveitis Reiter’s? • Acute, chronic, or recurrent, • Labs: • HLA-B27 (+ 70-90%) non-granulomatous AU • ESR is often elevated •ROS: • Often bilateral • Classic clinical signs 1. Urethritis • Male > females 2. Arthritis • 20-40 yo 3. Conjunctivitis (or Ant Uveitis) • Referrals: • Joint deformities • Urologist for urethral cultures, urine analysis • Rheumatologist for arthritis evaluation and possible • Urethral discharge imaging of the spine/joints

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What to Do if You Suspect Inflammatory Bowel Disease Inflammatory Bowel Disease?

• Includes: • Labs: – Ileo-Colitis (Crohn’s disease) – HLA-B27 • 2.4% will have anterior uveitis – Ulcerative Colitis • 5-12% will have anterior uveitis • Referrals: • Symptoms include abdominal pain, – Internal Medicine diarrhea, weight loss, fever, fatigue, joint pain – Gastrointerologist • 20% will have sacroiliitis • 60% will be HLA-B27 positive

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Psoriatic Arthritis Psoriatic Arthritis

• Diagnosis made by cutaneous • 7-25% changes, terminal joint • acute, chronic, recurrent inflammation, ungual non-granulomatous involvement anterior uveitis • Pts suffer with Conjunctivitis • Psoriasis with arthritis and anterior uveitis • Erythematous hyperkeratotic rash • Psoriasis may precede • Tissue swelling, distal joint arthritis by several yrs inflammation • Nail bed pitting (ungual •M = F changes), discoloration, thickening, cracking, • 40-50 yo ridging 69 70

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Ocular Treatment of the Uveitis of What to do if You Suspect +HLA-B27 Psoriatic Arthritis? • Aggressive Topical Steroids – Dosing every hour (12-14x/day with pred acetate 1% vs Durezol 4-6x/day) • Labs: • Cycloplegics • HLA-B27 • HLA-B27 AU recur and can be chronic • Recommended a 4 week treatment to lessen relapse • Referrals: • Occasionally need oral immunosupressive agents – Salazopyrine and methotrexate reduce recurrence? • Dermatologist – Properly educate patient • Rheumatologist • Get systemic work-up – Appropriate referral to subspecialty • We can make the diagnosis of an HLA-B27 related uveitis, but must rely on sub-specialty to confirm condition (ie: CRAP) – 50% of HLA-B27+ AAU will go on to develop one of the seronegative arthritis

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Non-Infectious Etiologies Sarcoidosis

Acute Chronic HLA-B27 Auto-immune Diseases •Ankylosing Spondylitis •Lupus • Multisystem •Reiter’s •Wegener’s granulomatous •Inflammatory Bowel (Colitis, Crohn) •Polychrondritis disease of unknown •Psoriatic Arthritis etiology Tubulointerstitial Nephritis Fuch’s Heterochromia Glaucomatocyclitis Crisis Idiopathic • Non-caseating Lens associated (phacolytic) Behcet’s granulomas form in Trauma and post-operative Sarcoidosis multiple systems Drug induced (Ribabutrin, Cidfovir) Juvenile Rheumatoid Arthritis (JRA) – composed of epitheloid Juvenile Idiopathic Arthritis (JIA) and giant cells Behcet’s Vogt-Koyanagi Harada Disease (VKH) – Granulomas secrete ACE Sarcoidosis Sympathetic Ophthalmia Idiopathic 73 74

• Most commonly characterized by: Sarcoid Presentation – bilateral hilar lymphadenopathy, • Inflammation: – pulmonary • Chronic iritis in 3-10% of all uveitis cases – Uveitis may be acute, recurrent or chronic infiltration • Posterior uveitis (choroditis, retinitis), perivascularitis, – dermatological optic neuritis manifestations • May be bilateral or unilateral • Females slightly more than males • Ocular involvement • 20-50 years of age, but may occur in children in 15-50%: as well – Uveitis; Orbital, lid, • African American 10-20x more than conjunctival www.uveitis.org Caucasians granulomas; dry eye 75 76

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• Lacrimal gland involvement occurs in 15- You Suspect Sarcoid? 28% of patients. • Exam: • Lacrimal gland – Careful evaluation of the conjunctiva and lacrimal glands looking for granulomas/nodules involvement – Skin nodules of eyelid, adnexa and systemic – painless, bilateral, palpable • Labs: swelling of the gland. – Elevated serum lysozyme, ACE levels • Moderate-to-severe • Other: keratitis sicca may result. – Chest x-ray or CT – Gallium scan • Posterior findings occur in – Tissue biopsy (lungs, lymph nodes, skin nodules, liver, 25-30% of patients with conjunctiva, lacrimal gland) – Pulmonary function tests sarcoidosis • Referrals: – Internal medicine – Pulmonologist – Ophthalmology for ocular nodule biopsy 77 78

Serum ACE Levels

• Cells that make up granulomas secrete • Combined use of ACE levels with large amounts of angiotensin converting enzyme (ACE), gallium scans increased the diagnostic • ACE levels are often high in patients with specificity in cases of clinically active sarcoidosis. systemic sarcoidosis from 83% to 99% • ACE levels, however, are not always high when compared to ACE levels alone. in sarcoidosis patients, – increased ACE levels can also occur in other illnesses • CSF ACE levels may be elevated in up • DM, COPD, hyperthyroidism, cancers to 50% of patients with neuro-sarcoid.

Serum Lysosome Treatment of Sarcoid

• The sensitivity of lysozyme for predicting • Systemic treatment: sarcoidosis was 79.1% vs 59% with ACE – steroids are the mainstay – NSAIDs may offer some benefit • Even in the cases without an elevated – Immunosuppressant agents serum ACE level, a value of 72.1% was • methotrexate, cyclosporine, and azathioprine obtained. • Ocular treatment of uveitis: • The serum lysozyme level demonstrated a – Topical steroids, cycloplegics – Due to chronic and recurrent nature, high risk significant tendency to increase with the of steroid complication number of organs involved (p < 0.01). • Cataract, GLC

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Infectious Uveitis

• In patients you suspect have an infectious etiology, caution with steroid treatment, especially systemic steroid treatment.

WHAT IS ONE OF THE SIDE EFFECTS OF STEROIDS?

– Should treat the underlying infection either first or in INFECTIOUS ETIOLOGIES conjunction with steroids. – Rely on lab studies, history, ROS, and the presence of granulomatous uveitis , posterior seg involvement

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Infectious Uveitis Bacterial Viral Fungal Parasitic Other Syphilis Syphilis Herpes Simplex Histoplasmosis Toxoplasmosis virus (HSV) Tuberculosis Varacella-zoster Candidiasis Toxocariasis virus (HZV) • Syphilis is a Lyme Disease Cytomegalovirus Aspergilliosis Cysticercosis multisystem, chronic (CMV) bacterial infection Endophthalmitis Epstein-Barr Cryptococcosis Diffuse unilateral virus (EBV) subacute caused by the neuretinitis (DUSN) spirochete Leptospirosis Rubella coccidioidomycosis Onchocerciasis Treponema pallidum

Ocular West Nile Virus nocardiosis (WNV) Bartonella Adenovirus henselae Mononucleosis Influenza 98 99

CDC Primary and Secondary Syphilis •In US • 2000, 2.1 cases per 100,000 • It is associated with • 2011, 4.5 per 100,00 multiple ocular • 2013, 5.3 per 100,000 • In Illinois (ranked 9th of 50 States) manifestations that • 6.2 per 100,000 occur in both the •In CA (2nd) • 9.3 per 100,000 acquired and • Georgia (1st) congenital forms • 10.3 per 100,000 • District of Columbia • 26.6 per 100,000 • Wyoming (50th) • Transmission occurs • 0.2 per 100,000 via sexual contact or • Kansas (41st) transplacental • 1.8 per 100,000

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Primary and Secondary Syphilis—Rates of Reported Cases by State, United States and Outlying Areas, 2014

NOTE: The total rate of primary and secondary syphilis for the United States and outlying areas (Guam, Puerto Rico, and Virgin Islands) was 6.4 per 100,000 population.

2014-Fig 35. SR, Pg 35

Primary and Secondary Syphilis — Reported Cases* by Sex, Sexual Behavior, and 2013 Syphilis Rates Race/Ethnicity, United States, 2014

*Of the reported male cases of primary and secondary syphilis, 18.8% were missing sex of sex partner information; 3.3% of reported male cases with sex of sex partner data were missing race/ethnicity data. † MSW = men who have sex with women only; MSM = men who have sex with men.

2014-Fig 42. SR, Pg 38

Primary Syphilis Syphilis • The predominant lesion of primary syphilis is a • Accounts for 1-2% of uveitis cases, but chancre at the inoculation is considered the great masquerader site. • Chancres • Three stages of infections: – erythematous papules at the – Primary, secondary, latent progressing to inoculation site that later erode to form painless ulcers. tertiary • The lesions appear 4 weeks after the initial infection and heal spontaneously in 1-2 months.

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Primary Syphilis Secondary Syphilis

• After T pallidum • The systemic penetrates the skin or treponemal load is largest in secondary mucous membrane, syphilis. the organism enters • Generalized the lymphatics and maculopapular (or blood stream and pustular rash), and disseminates shortly lymphadenopathy are the characteristic after contact. lesions in this stage. • If left untreated, • These lesions appear 4- primary syphilis leads 10 weeks after the initial to secondary syphilis manifestation.

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Secondary Syphilis • Constitutional symptoms Latent Syphilis of fever, malaise, headache, nausea, anorexia, and joint pains • Early Latent often are present. – occur within 1 year after initial infection,

• The liver, kidneys, and/or GI tract may or may not • Late Latent be involved. – After 1 year of the initial infection

• Ocular involvement has • Most cases have been reported to stay at been reported in 10% of cases, and cerebrospinal the latent stage with 30% converting to the fluid (CSF) pleocytosis tertiary stage. has been seen in a few cases. 110 111

Tertiary Syphilis Ocular Syphilis

• 3 sub-groups: • Rarely occurs before 6 months after the – Benign tertiary primary infections • presents with gummatous lesions that are actually granulomas histologically; in the skin and the mucous membranes, the choroid, ciliary body, and iris • Most ocular involvement occurs during – Cardiovascular the secondary, Latent or tertiary stages • presents with involvement of the coronary arteries or the aorta. • Uveitis may be acute, chronic or – Neurosyphilis recurrent • Manifest with tabes dorsalis or general paresis • CNS is affected via the vascular pathways or via direct – Usually granulomatous, but may also be involvement of parenchyma. non-granulomatous

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Making the Diagnosis Making the Diagnosis

• Labs: • Labs: – Non-treponemal serology tests • RPR or VDRL – Treponemal serology tests – Are antibodies present for treponema palidium? – Indicate disease activity by quantifying amount of • FTA-ABS or MHA-TP anticardiolpin antibody in serum – Reactive or nonreactive • Reactive or nonreactive at dilutions of 1:1, 1:2, 1:4, 1:8, 1:16, 1:32, 1:64, etc • Will test positive after primary infection • 50-75% can be nonreactive in early primary syphilis (<3 wks) indicating either active or past infection • 100% reactive 4+ weeks after exposure, secondary, early latent • Referrals: • Can be negative in late syphilis • Most often used as a screening test – Internal medicine and/or infectious disease

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Treatment for Syphilitic Uveitis Review

• Must determine what stage the infection is in Stage Manifestations Uveitis Present? before determining treatment: – Congenital: Primary Chancer No • IV penicillin – Primary, secondary, or early latent: Secondary Rash, Yes • Single dose IM PCN Lymphadenopathy – Late Latent or tertiary: Latent No evidence of Yes, most common • IM PCN weekly x 3 doses systemic disease – Neurosyphilis: Tertiary Cardiovascular syphilis, Yes • IV PCN q4hrs for 10-14 days neurosyphilis, • Using oral steroids without PCN may lead to Benign tertiary syphilis exacerbation of the disease! *Foster CS. Diagnosis and treatment of uveitis

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Infectious Uveitis Bacterial Viral Fungal Parasitic Other Tuberculosis Syphilis Herpes Simplex Histoplasmosis Toxoplasmosis virus (HSV) Tuberculosis Varacella-zoster Candidiasis Toxocariasis • Granulomatous virus (HZV) Lyme Disease Cytomegalovirus Aspergilliosis Cysticercosis infection caused by (CMV) Mycobacterium Endophthalmitis Epstein-Barr Cryptococcosis Diffuse unilateral tuberculsis virus (EBV) subacute neuretinitis • Primarily affect the (DUSN) lung, but may affect Leptospirosis Rubella coccidioidomycosis Onchocerciasis Ocular West Nile Virus other systems (eye). nocardiosis (WNV) – The bacterium likes Bartonella Adenovirus highly oxygenated henselae structures! Mononucleosis Influenza 118 119

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Ocular Involvement

• May be due to active infection or immunologic reaction to the organism – Scleritis – Phlyctenulosis – interstitial keratitis – granulomatous uveitis (anterior and/or posterior)

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Treating TB Making the Dx of Tuberculosis • Systemic treatment • Labs: – Initial 2-month combination course: – PPD (Purified Protein Derivative) skin test • Positive indicates exposure • Isoniazide (INH), rifampin, and pyrazinamide daily. • Does not tell you if there is active infection Ethamutol is added in more resistant TB. – Interferron gamma/QuantiFerron • Used for those who have previously test +PPD – Continuation phase for an additional 4-7 months with isoniazide and rifampicin – Chest x-ray – For latent TB, 6-9 mos of isoniazide – Bacterial culture or PCR • Referral: • Ocular treatment: – Internal medicine and/or infectious disease – Steroids ideally post-systemic treatment or in conjunction with systemic therapy 126 127

Infectious Uveitis

Bacterial Viral Fungal Parasitic Other Syphilis Herpes Simplex Histoplasmosis Toxoplasmosis virus (HSV) Tuberculosis Varacella-zoster Candidiasis Toxocariasis • 86% of TB cases in 2014 had known virus (HZV) HIV status at TB diagnosis. Lyme Disease Cytomegalovirus Aspergilliosis Cysticercosis (CMV) • All TB patients should have counseling Endophthalmitis Epstein-Barr Cryptococcosis Diffuse unilateral virus (EBV) subacute and testing for HIV infection neuretinitis (DUSN) Leptospirosis Rubella coccidioidomycosis Onchocerciasis Ocular West Nile Virus nocardiosis (WNV) Bartonella Adenovirus henselae Mononucleosis Influenza 130

Lyme Disease CDC by State

• Bacterial infection caused by the Borrelia burgdorferi spirochete and spread via tick bites. • Animal reservoirs: deer, horses, cows, rodents, birds, cats, dogs. • 8.2/100,000 • Men > females • 2 age groups: – 5-14yo – 25-50yo • Peak time for infection: May-August • In most cases, the tick must be attached for 36 to 48 hours or more before the Lyme disease bacterium can be transmitted.

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Lyme Disease by Month

From left to right, an Ixodes scapularis larva, nymph, adult male tick, and adult female tick. Illustrative examples of culture-confirmed erythema migrans.

Gary P. Wormser et al. Clin Infect Dis. 2006;43:1089-1134 Gary P. Wormser et al. Clin Infect Dis. 2006;43:1089-1134

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3 Stages of Lyme Disease Lyme Disease • Stage 1: – Macular rash • Stage 2: (erythema migrans) at the site of the tick – Occurs weeks-months following exposure bite. where the spirochete spreads to the skin, – Within 2-28 days in CNS, joints, heart, and eyes. 60-80% – Neurological involvement in 30-40% – Rash may take (meningitis, encephalitis, Bell’s Palsy) “Bull’s Eye” pattern – Ocular include anterior, posterior, –Symptoms: intermediate and pan uveitis • Fever, malaise, fatigue, myalgias, – 25% of new onset Bell’s is from Lyme arthralgias

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• Stage 3 or persistent disease – Occurs 5 or more months after the infection – Multiple cranial nerve involvement (II, III, IV, V, VI, VII). – Keratitis is most common ocular finding in stage 3 followed by episcleritis

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Recommended antimicrobial regimens for treatment of patients with Lyme disease.

Gary P. Wormser et al. Clin Infect Dis. 2006;43:1089-1134

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Recommended therapy for patients with Lyme disease.

If you Suspect Lyme… • Labs: – Lyme (IFA) immunosorbent assay –ELISA – Western Blot series –PCR • Systemic treatment: – Doxycycline except in children or pregnant • Adults: 100 mg bid for 10-21 days • Kids over 8years old: 4 mg/kg per day bid with max of 100 mg per dose – Amoxicillin in kids, pregnant • Adults: 500mg tid for 14-21 days • Kids: 50mg/kg per day tid with max dose of 500mg/dose – Cefuroxime axetil • Adults: 500mg bid 14-21 days • 30 mg/kg per day bid with max dose of 500 mg per dose • Ocular Treatment: – Topical steroids for uveitis after or in conjunction with systemic Gary P. Wormser et al. Clin Infect Dis. 2006;43:1089-1134 treatment © 2006 Infectious Diseases Society of America 146

Infectious Uveitis Most Common Infectious Bacterial Viral Fungal Parasitic Other Underlying Etiology for AU Syphilis Herpes Simplex Histoplasmosis Toxoplasmosis virus (HSV) Tuberculosis Varacella-zoster Candidiasis Toxocariasis virus (HZV) • Viral Etiologies Lyme Disease Cytomegalovirus Aspergilliosis Cysticercosis (CMV) – HSV & VZV=up to 10% Endophthalmitis Epstein-Barr Cryptococcosis Diffuse unilateral –CMV virus (EBV) subacute neuretinitis • HIV negative: 22.8% of AU associated with (DUSN) raised IOP* Leptospirosis Rubella coccidioidomycosis Onchocerciasis Ocular West Nile Virus – Rubella nocardiosis (WNV) • Fuch’s Heterochromia Iridocyclitis Bartonella Adenovirus henselae Mononucleosis Influenza *Chee SP, Bacsal K, Jap A, et al. Am J Ophthalmol 2008;145:834–840. 147

HSV and VZV Clinical Features Clinical Features of Viral AU?

• Corneal scars • May vary depending on the Virus • Corneal hypo-aesthesia • 50-90% of all types of viral AU: • Sectoral iris atrophy • Elevated IOP – Elevated IOP •KP – Can be granulomatous, but – Iris atrophy usually smaller KP (non- granulomatous) –KP – located centrally or in Arlt’s Triangle – Unilateral – Medium to fine KP have been seen • Often confused with Posner– Schlossman syndrome (PSS)

Jap and Chee. Curr Opin Ophthalmol 2011:22:483-488

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Treatment of HSV Uveitis Comparison of Herpetic Uveitis • Topical Steroids – ie: 1% prednisolone acetate ophthalmic suspension QID HSV VZV • Concurrent anti-viral!! • Location: • Location: – 61% anterior with keratitis – 58% anterior with keratitis – Viroptic® (1% trifluridine ophthalmic solution) QID – 20% without keratitis – 17% without keratitis – Zirgan® (ganciclovir ophthalmic gel) 0.15% QID • Type: • Type: – Non Granulomatous 80% – Non Granulomatous:96% *******oral anti-viral (preferred)******* – Granulomatous 20% – Granulomatous : 4% • Valcyclovir 500mg BID • Course: • Course: • Acyclovir 400-800mg 5x/day – Acute: 11% – Acute: 20% – Chronic: 18% – Chronic: 42% • Less ocular toxicity with oral antivirals – Recurrent: 71% – Recurrent: 38% • contraindications (pregnancy). • Iris Atrophy: 41% • Iris Atrophy: 25% • Unilateral vs. Bilateral: • Unilateral : 100% • Cycloplegic agents – 82:18 • Past h/o zoster • Long-term/Chronic oral antivirals to reduce recurrence rates. 151 – Year or more of tx 152

Subgroup HEDS Study: The Role Treatment of zoster of Oral Acyclovir (HZV/VZV) Uveitis • Anti-viral therapy • 45% decrease in recurrence in ALL forms of – valcyclovir (Valtrex) HSV (epithelial, stroma, iridocyclitis) – Acyclovir • Effect was best demonstrated in patients with • Steroids helpful, but relapses high if not multiple recurrences treated concurrently with anti-virals • NO decrease in incidence of changing to • Control IOP stromal HSV – up to 90% have high IOP • NO effect acutely but decreased recurrence – How to lower IOP?

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Treatment of zoster Anti-Viral Dosing? (HZV/VZV) Uveitis • HEDS* interpretation for active ocular disease: • Treat Inflammation – *acyclovir, 400 mg five times per day • Treat with Antivirals – valacyclovir, 1000 mg twice per day • Control IOP – famciclovir 250 mg three times per day. – up to 90% have high IOP • Maintenance/prophylaxis to reduce recurrence: – How to lower IOP? • Can I use a PGA? – acyclovir, 400 mg twice per day – valacyclovir, 500 mg daily.

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Will PGA Re-activate HSV?

• Purpose: – To determine the reactivation rate of HSV keratitis for pts treated with PGA • Results: – the rate of HSV was 0.11% – Similar rate to normal population (0.15%) – No correlation with an increased risk from the use of PGA.

Beam G, Reardon G, Zimmerman TJ. J Glaucoma. 2004;13:361–4.

CMV AU Features

• Patchy or diffuse iris atrophy • No posterior Synechiae • Posterior Segment is usually spared – Different clinical presentation from CMV retinitis which occurs in immunocompromised pts. • Thought to be an underlying cause of PSS

Jap and Chee. Curr Opin Ophthalmol 2011:22:483-488

Treatment of CMV Uveitis

• Studies comparing oral and topical ganciclovir – 75% of pt treated with orals responded BUT 3 out of 4 relapsed – 66% responded to topical ganciclovir • 25% of chronic recurred – Recommendation: • Topical ganciclovir for suspected CMV AU in combination with topical steroids

*Chee SP, Jap A. Cytomegalovirus anterior uveitis: outcome of treatment. Br J Ophthalmol 2010; 94:1648–1652.

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Rubella Anterior Uveitis

•KP – Fine, diffuse, stellate KP • Diffuse Iris Atrophy and/or Heterchromia • No PAS • PSC •Vitritis • Posterior Seg involvement – Sectorial peripheral retinal vascular leakage –CME – Disc hyperfluorescence on FA. • AKA: Fuch’s Heterochromia Uveitis

Is it Possible to Differentiate Between Infectious and Non-Infectious KP?

Is it Possible to Differentiate Between Infectious and Non-Infectious KP? • In vivo confocal microscopy* – Classify KP based on appearance • Globular • Infiltrating** – Infectious • Smooth-rounded – Granulomatous • Stippled • Dendritiform** – Infectious • Crusciform – **more common in infectious uveitis – **Sensitivity/specificity=84% and 93%

*Mahendradas P, Sheety R, et al. Ophthalmology. 2010;117:373-380.

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Treatment for Rubella Uveitis Recommendation

• Respond poorly to steroids. • A virus cause should be suspected in • Primary goal is to control IOP and cases of unilateral anterior uveitis with prevent loss of vision iris atrophy and elevated IOPs – Glaucomatous optic atrophy • Judicious use of corticosteroids if – PSC aqueous analysis (PCR) is not • CE/IOL available. – CME risks • Concurrent anti-virals is appropriate and recommended

Thank You!

Last but not Least… [email protected] IDIOPATHIC AKA: UNDETERMINED

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Detecting Functional Glaucoma Change in Progressing  Many different conditions having in common a Glaucoma. characteristic optic neuropathy usually associated with a higher than normal intraocular pressure.

Guided Progression Analysis (GPA)

Paul M Munden, MD MBA Associate Professor University of Kansas Department of Ophthalmology

Glaucoma: Diagnosis Glaucoma: Diagnosis

 Characteristic optic nerve changes on clinical  Clinical examination examination  Increased vertical cup to disc ratio  Focal notching and rim thinning  Characteristic Nerve Fiber Layer (NFL) changes on optic  ISNT guideline nerve OCT (structure)  Concentric increase in cup to disc  Characteristic field loss on automated perimetry ratio (functional)  Disc hemorrhage

Glaucoma: Diagnosis  Nerve Fiber Layer Changes Glaucoma: Diagnosis  Thinning or loss of NFL in characteristic locations  Visual Field Loss  Correlation to NFL anatomic structure  Arcuate Defects  Nasal Step  Cecocentral scotoma (LTG) Glaucoma: Diagnosis

 Automated Perimetry

 Humphrey Visual Field Analyzer

 Stat PAC

 Single Field Analysis

Glaucoma Diagnosis Glaucoma: Progression Set IOP Goal

Initiate and Optimize  NFL loss is irreversible and permanent Therapy

 Untreated or inadequately treated glaucoma will Monitor IOP progress Disc Photos ON OCT Automated VF  Goal is to lower IOP to a level sufficient to prevent further damage Stable Progression  Monitor and test patient at regular intervals to detect progression or confirm stability Confirm Progression

Add or Alter Reset GPA Therapy Baseline Fields

How Often Does Glaucoma Progress? Untreated Glaucoma: Visual Disability Study N Follow-up % Progression (years)  Population Survey Tx No Tx  St. Lucia, West Indies Clinic Based  10 year resurvey OHTS 1636 54.4%9.5% EGPS 1081 5 13.4% 14.1%  205 untreated glaucoma patients and suspects EMGT 255 6 45% 62%  16% progressed to blindness in at least 1 eye CNTGS 140 eyes 7 12% 35% CIGTS 607 5 10.7%-13.5% N/A  9% progressed to blindness in both eyes 8 21%-25% N/A  More than 50% that progressed to end-stage had minimal AGIS 747 eyes 8-13 28.1%-32.5% N/A or no visual field loss at baseline

Population Based St.Lucia 205 10 N/A 52%-73% Wilson, et al. Am J Ophthalmol. 2002 Sep;134(3):399-405. Treated Glaucoma: Visual Disability Glaucoma: Detecting Progression

 Retrospective Study  Structural Changes from Baseline  Olmstead County, MN  Serial Disc Photography  20 year follow-up  Visual inspection

 295 newly diagnosed treated patients.  Serial Optic Nerve OCT  IOP not optimally controlled  Visual inspection  Image analysis software guidance  Probability of blindness after 20 years (Kaplan-Meier)  BCVA 20/200 or worse, <20 degrees visual field  One eye – 27% (95% CI 20-33%)  Functional Changes from Baseline  Both eyes – 9% (95% CI 5-14%)  Serial Automated Visual Field Testing

Hattenhauer, Ophthalmology. 1998 Nov;105(11):2099-104

Visual Field: Test-Retest Variability Glaucoma: Visual Field Progression  Frequency of seeing curve  Scotoma depth and location

 Difficult to detect ”real” change!  Overall VF status  Less variability with minimal or severe loss  Inherent variability in test to test performance  Test strategy  OHTS  Full threshold

 CNTG  External Factors  As many as 4 to 6 abnormal VF necessary to confirm  Inexperienced technicians progression  Room temperature  Chair position/comfort

Glaucoma: Visual Field Progression Is there a tool to help us?

Is there a way to distinguish true  Difficult to detect change! visual field progression from  Inspection of serial fields normal variability?  Which fields compare?  What parameters? Guided Progression Analysis (GPA) Guided Progression Analysis (GPA)

 HVF Analyzer software package  GPA Normative Database  363 subjects  Identify and measure statistically significant VF  Diverse by gender and ethnicity progression for glaucoma patients  Mild to Severe glaucoma  Compares two designated baseline VF tests with up to  Excludes first time test takers 14 follow-up visual field tests.  4 clinic visits in 1 month   Reports progression when VF results fall outside 3 fields per visit expected range of test-retest variability  Full Threshold, SITA Standard, SITA Fast

Guided Progression Analysis (GPA)

Event Analysis Trend Analysis

 Progression analysis plot  Visual Field Index (VFI) regression analysis  Pointwise variability in Pattern Deviation plot  VFI values are plotted to determine rate of  Identifies individual points progression and statistical or groups of points that are significance statistically worse  Provides a visual trend of  Based on EMGT trial the progression pattern and criteria predicts VFI loss over time

Guided Progression Analysis (GPA) Permitted Baseline and Follow-up Configurations Using GPA for GPA  Software Activation If the Key Exam is: And Baseline Exams Follow-up Exams must are: be:  Set up Print Out Options SITA Standard SITA Standard All SITA Standard  GPA reports

 Select Baseline Fields SITA Standard Full Threshold Any combination of SITA  Use VFI plot to help select similar baseline fields Standard and Full Threshold  Oldest two automatically chosen unless:  Learning effect SITA Fast SITA Fast All SITA Fast  False Positives > 15%  Select new baseline fields after change in treatment or SITA Fast Full Threshold Any combination of SITA confirmed progression from baseline Fast and Full Threshold

 Compares subsequent fields to baseline fields  Statistical analysis to determine likely progression Guided Progression Analysis (GPA) GPA Reports

 Full GPA Report  The whole ball of wax.  Baseline page with grayscale and indices including VFI plot  All follow-up exams (up to 14) with Progression Probability Analysis and GPA alert

 GPA Last 3 Follow-Up  Full GPA lite  Baseline page and three most recent follow-up exams

Guided Progression Analysis (GPA) GPA Reports

 Single Field Analysis with GPA  Standard SFA with greyscale and key indices  Separate GPA information box with Progression Analysis Probability plot  No VFI plot or linear regression analysis  GPA Summary Report  Baseline fields with grayscale and indices at bottom  VFI plot and VFI bar in center  Current visual field with grayscale and indices at bottom  Progression Analysis Probability Plot and GPA alert at bottom

Guided Progression Analysis (GPA) Interpreting Reports - Event Analysis  Deviation from Baseline Plot  Compares pattern deviation of f/u test to average pattern deviation of baseline tests at each point

 Progression Analysis Probability Plot  Point by point statistical significance of values in Deviation from Baseline Plot  Single dot – no significant change  Open triangle – P< 5% (.05,1/20) real deterioration at the point  Average of 2-3 points (out of 76) by chance alone  Half filled triangle – P<0.5% same point, two consecutive tests  Solid triangle – P< 5% same point, three consecutive tests.  X – Data out of range for analysis.  Areas of deep or absolute defect. Guided Progression Analysis (GPA) Interpreting Reports - Event Analysis

 GPA Alert  Alerts to deterioration in consecutive tests

 Applies to whole field, not individual points  No Progression Detected  Possible Progression – 3 or more points, 2 consecutive tests  Likely Progression – 3 or more points, 3 consecutive tests

 EMGT criteria

Guided Progression Analysis (GPA) Interpreting Reports - Trend Analysis  VFI Plot  Graphs VFI values as a function of patient age  Linear regression analysis of VFI over time  At least 5 exams over 2 years  Not drawn when slope is positive  Learning Effect  Not drawn when 95% confidence level on slope >5%

 VFI Bar –  Histogram indicates current VFI value and 2 – 5 year VFI projection of the linear progression line.  VFI 50% in better eye or less correlates with significant VRQOL impairment

Peters, Heijl, et al. Acta Ophthalmol. 2015 Dec; 93(8):745-52

Guided Progression Analysis (GPA) Interpretation  Statistically based software package to help identify glaucoma progression  Requires sufficient number of fields  At least 5 for event analysis  At least 5 over 2 years for trend analysis  Choose good baseline fields  Garbage in, Garbage out  Reset after progression or intervention  Systematic Inspection of Report  Assess the triangles  Check defect depth, location, RNFL anatomy correlation  If progression called, check fields for reliability Guided Progression Analysis (GPA) Guided Progression Analysis (GPA) Interpretation Summary

 GPA vs “Experts”  Not a substitute for Glaucoma Diagnosis clinical judgment Set IOP Goal  “Level of agreement between majority expert consensus of  Aid to analysis, helps Initiate and subjective determination of visual field progression and differentiate Optimize Therapy GPA is “fair.” In cases of disagreement with GPA, the expert variability from Monitor consensus was usually progression. Access to GPA results IOP progression Disc Photos ON OCT after initial classification changed expert consensus in 11 Automated VF of 100 cases.”  Correlate with other clinical findings Stable Progression  Tanna, Budenz, et al, Ophthalmology. 2012 March; 119(3):468-473

Confirm  Treat the patient not Progression the test! Add or Alter Reset GPA Therapy Baseline Fields