4/15/2019 4/15/2019

Hydroxychloroquine: An Ophthalmic Update Alex D. Gibberman, OD FAAO Harpers Point Associates Cincinnati OH

Financial Disclosure

• Acculens- speaker/consultant • Eaglet- speaker/consultant

1. No baseline testing Case 1: 2. Dosing is considered high risk given weight

• 28 year old Caucasian female • Diagnosed years ago with severe systemic Lupus 3. Duration of therapy • Multiple organs involved Red flags? • Using hydroxychloroquine x 8 years 400mg/day • Patient weight = 110 pounds (50kg) 4. Unusual to see use of Chloroquine and • Rheumatologist added Chloroquine as well x 4 years…dose unknown Hydroxychloroquine together at high doses • First time patient seeing an eye doctor in years. • Progressive vision loss past few years. 5. No annual or semi annual testing in high risk patient

1 2 4/15/2019 4/15/2019

Findings • Chloroquine

• BCVA: • Hydroxychloroquine • OD 20/150 • Amiadarone • OS 20/200 • Indomethacin • Anterior segment • Verticillata • Tamoxifen • Remember CHAI T • Post Segment • + Fabry’s Disease • Bullseye mac ou • Central field scotoma Corneal Verticillata

Not my Early • Verticillata of patient, but

example of Summary of • Thinning of OUTER found on OCT (IS/OS jxn) fields Possible Signs Moderate • Paracentral field defect (except Asian of Toxicity decent)

• Advanced thinning/loss of Photoreceptor line on OCT Late • Central vision affected • Visible pigmentary changes around macula (bullseye)

So What? This is rare isn’t it? More examples

3 4 4/15/2019 4/15/2019

A. 400,000 How Many People in USA take B. 1.4 Million Plaquenil What is the 2019 Actual Incidence C. 5 Million of Toxicity?

5 MILLION PEOPLE What is the Actual Incidence of Toxicity?

• What quantifies toxicity? • Vision loss?

• Repeatable field defect?

• Visible retinal changes?

• OCT thinning of the macula with progression?

Hydroxychloroquine Use Risk Guidelines

• Uses: • 2002 guidelines for high risk: • malaria, Rheumatoid Arthritis, Systemic Lupus,sjogren’s disease and other • >5 years , cumulative dose of 1000g, >6.5mg/kg of ideal body weight, age, autoimmune inflammatory conditions liver/kidney disease, other retinal disease, • No real testing guidelines.. • 2018 was the 135th most commonly prescribed medication • 2011 guidelines included more testing suggestions • 5 million Rx’s in the United States • 10-2 central fields, photography/Fundus Autofluorescence, dilated • Its cheap… avg per patient cost was < $25/month exams • Other tests: multifocal ERG, color testing, amsler grid • (for comparison, Prednisone was 136th, timolol was 142nd, methotrexate was 152nd)

5 6 4/15/2019 4/15/2019

2016 Guidelines/Findings (most recent) What is the OUTER RETINA?

Bullseye maculopathy is LATE stage finding. • May be defined slightly differently in different OCTs

Asians don’t follow typical paracentral Screen with 24-2 fields instead of 10-2 pattern • Typically External limiting membrane to the RPE • This includes the PIL line that is crucial in toxic Dosing from rheumatology now done by actual, not ideal body weight maculopathy • This is what we need to follow!!!!! If patient taking more than 450mg plaquenil daily, they are high risk >5mg/kg/day = higher risk. Ex: 200lb Most common dose is 200 bid or 400 daily. man = 90 kg 90x5 = 450 Ex 2: 115 lb female = 52kg 52x5=260mg if this person is taking same dose as abo ve th e y are h igh risk.

Duration/cumulative dose is still biggest risk factor • After 20 years of use, toxicity is found in 1 in 5 Stuff to Remember people!!!!!!!!!! • Liver/kidney disease or existing retinal disease increases risk • Average CENTRAL macular thickness is 250um 2016 • Tamoxifen use (remember CHAI T) increases risk • parafovea is thicker • 3-6 month half life theory went out the window… • Toxic maculopathy affects OUTSIDE foveal Guidelines/Findings center first (most recent) 2016 guidelines for testing/screening • Toxic maculopathy = ATROPHY of OUTER retina • Pay attention to “other stuff” that may affect • Baseline 10-2 field (24-2 in Asians) and OCT macula + thickness dilated exam • ERM, VMT, ARMD etc • Annual testing not required in LOW risk patients until 5 • Separate outer retina years on medication • Visible fundus findings are LATE stage and are not considered vital to the screenings.

What should you do now? ELM RPE

• Be preventative, not reactive • Look at medication lists for your patients! • At minimum: • Baseline OCT macula, central 10-2 field (24-2 for Asians) • dose and duration. • High risk vs low risk (elderly, liver/kidney disease, weight, dose, other retinal disease) • progression analysis of OUTER RETINA ONLY of macula OCT • Low risk = yearly OCT mac and fields after 5 years, 2x yearly after 10 • High risk = yearly or 2x yearly after 5 years.

7 8 4/15/2019 4/15/2019

Examples

Toxic or Not Toxic Toxic or Not Toxic

• 100kg male. Taking 400mg/day x 15 years • 37 year old female • No other pertinent medical history • Medical history: hx of • Will this OCT show central thinning alcohol/substance use, liver • YES • TOTAL centralmacular thickness function…probably not good • THIN • Inner Retinal Thickness • Medication history: unknown • Centrally THIN • Parafovea actually would look thicker due to ERM • Occupation • Singer, entertainer, • Outer Retinal Thickness • NORMAL questionable decision maker

Toxic or Not Toxic

• 50kg female. 200mg/day • 74 years old, 10 years on plaquenil A Very Quick • Smoker • No other pertinent hx or meds Scleral Update • Risks? • Age, Duration

9 10 4/15/2019 4/15/2019

Review of Uses

• Keratoconus/Pellucid • Salzmann's • High Ammetropia • Post-surgical Irregular astigmatism • Corneal opacities • Exposure keratitis • Dry Eye • Presbyopia

New Technology

• SCLERAL topographers- measure out to 20mm • Eaglet – Eye Surface Profiler • Fluorescence based profilometry • Based on elevation maps • Non company specific-->works with many designs • Visionary Optics – S-map 3D • Fluorescence based imaging • Europa scleral lens • Pentacam • Now capable of measuring sagital height • Scheimflug image not requiring flourescein

11 12 4/15/2019

Eye Surface Profiler: Bisphere Elevation Map

13