© 2017 American Medical Association. All rights reserved. · Association between long-lasting...

Supplementary Online Content 1 The Multicenter Uveitis Steroid Treatment (MUST) Trial and Follow-up Study Research Group. Association between long-lasting intravitreous fluocinolone acetonide implant vs systemic anti-inflammatory therapy and visual acuity at 7 years among patients with intermediate, posterior or panuveitis. JAMA. doi:10.1001/jama.2017.5103 eAppendix. The Multicenter Uveitis Steroid Treatment (MUST) Trial and Follow-up Study Research Group, Credit Roster eTable 1. Incident Ocular and Systemic Adverse Outcomes for Eyes/Patients Utilizing Assigned Therapy eTable 2. Quality of Life Outcomes for Participants Randomized to Implant or Systemic Therapy eFigure 1. Treatment Patterns for Eyes With Uveitis Assigned to (a) Implant or (b) Systemic Therapy eFigure 2. Distributions of (a) Weight and (b) Change in Weight From Randomization for Participants by Treatment Assignment This supplementary material has been provided by the authors to give readers additional information about their work.

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eAppendix. The Multicenter Uveitis Steroid Treatment (MUST) Trial Research Group, Credit Roster

Participating Clinical Centers

Duke Eye Center, Durham, NC: Glenn J. Jaffe, MD (Director); Michael Allingham, MD; Cristina F. Bunn; LaToya Greene; Sean Grout; Michael Hughes; Ryan Imperio; Tiffanie Keaton; Michael P. Kelly; Eleonora (Nora) M. Lad; Paola Perez; Lauren Welch; Former Members: Claxton Baer, MD; Brenda Branchaud, COT; Joyce Bryant, COT; Sai Chavala, MD; Michael Cusick, MD; Shelley Day, MD; Pouya Dayani, MD; Justis Ehlers, MD; Paul Hahn, MD, PhD; Muge Kesen, MD; Larry Koreen, MD, PhD, MPH; Annie Lee, MD; Phoebe Lin; Alex Melamud, MD; Brian Lutman; Joseph Nissim Martel; Jawad A. Qureshi, MD; Adrienne Williams Scott; Neha (Shah) Serrano, MD; Cindy Skalak, RN, COT; Robert F. See, MD; Robert K. Shuler, MD; Lejla Vajzovic, MD; Megan Wood, MS, COA. Emory University, Atlanta, GA: Steven Yeh, MD (Director); Alcides Fernandes, MD; Deborah Gibbs, COMT, CCRC; Donna Leef, COMT. Former Members: Daniel F. Martin, MD; Sunil Srivastava, MD. Johns Hopkins University, Baltimore, MD: Jennifer E Thorne (Director), Joseph Belz; Jeff Boring, COA; Kristen L. Brotherson, BS; Bryn Burkholder, MD; Dennis Cain; Russ Distler; David Emmert; Janis R. Graul; Charles Mark Herring; Dana Hornbeak, MD; Irfan Khan; Jacquelyn McDonald; Kelly Miller; Robert Moore; Ahmadreza Moradi, MD; Abhishek Naidu, BSC; Antonia Nwankwo, BS; Ashvini A Reddy, Terry Reed, COA; Nicholas Rhoton; Amde S. Shifera, MD, PHD. Former Members: Ellen Arnold, BS; Patricia M. Barnabie, BS; Hosne Begum, MBBS, MPH; Marie-Lynn Belair, MD; Stephen G. Bolton, CRNP; Joseph B. Brodine; Diane M. Brown, MSN, RN; Lisa M. Brune, BSN, RN; Nicholas J. Butler, MD; Mary A. Cook, BA, MS; James P. Dunn, MD; Anat Galor, MD; Theresa Gan, MD; Adam Jacobowitz, MD; Meera Kapoor; Sanjay Kedhar, MD; Stephen Kim, MD; Ashley Laing, MD; Henry A. Leder, MD; Theresa G. Leung, MD; Alison G. Livingston, BSN,RN; Michael C. Mahon, BS; Yavette Morton; Kisten Nolan, BSN, MPH, RN; Trucian L. Ostheimer, MD; George B. Peters, MD, MBA; Priscilla Soto; Ricardo Stevenson, MD; Michelle Tarver-Carr, MD, PhD; Yue Wang, MD, PhD. Massachusetts Eye Research and Surgery Institute, Cambridge, MA: C. Stephen Foster, MD (Director); Linda Bruner; Amanda Goggin; Stacey Lee; Halea Meese, MS; Jarrod Needle; Marianny Quezada; Hyun Seonwoo, BS. Former Members: Sarah Acevedo, MD; Stephen D. Anesi, MD; Fahd Anzaar, MD; Olga Ceron, MD; David M. Hinkle, MD; Tom Cesca; Angelica Contero; Kayleigh Fitzpatrick; Faith Goronga; Jyothir Johnson; Karina Q. Lebron, MD; Danielle Marvell; Chandra Morgan; Nita Patel, MSW; Nancy Persons; Jennifer Pinto; Sana S. Siddique; Janet Sprague; Bailey Wentworth, MS; Taygan Yilmaz. National Eye Institute, Bethesda, MD: H. Nida Sen, MD, MHSc (Director); Akshar Abbott, MD; Mike Arango; Matt Atkinson; Karen Armbrust, MD, PhD; Michael Bono; Faith Chen, BSN, RN; Denise Cunningham, CRA; Darryl Hayes, COA; Jared Knickelbein, MD, PhD; Shilpa Kodati, MD; Dessie Koutsandreas, BS, COA; Rob Mays; Leanne Reuter, COA; Patti Sherry, MSHS, BSN, CCRP. Former Members: Allison Bamji, RN; Hanna Coleman, MD; Geetaniali



Davuluri, MD; Lisa Faia, MD; Chloe Gottlieb, MD; Guy V. Jirawuthiworavong, MD; Julie C. Lew, MD; Richard Mercer, COT; Robert B. Nussenblatt, MD; Patti Dominic Obiyor, BSN; Cheryl H. Perry, BSN; Natalia Potapova, MD; Gregory L. Short, COMT; Wendy Smith, MD; Alana Temple, BSN Eric Weichel, MD; Keith J. Wroblewski, MD; Steven Yeh, MD. New York Eye & Ear Infirmary, New York, NY: Paul A. Latkany, MD (Director); Maya Ben-Zeev; Corinne Coonan; Andrea Honda, MD; Monica Lorenzo-Latkany, MD; Robert Masini, MD; Azinda Morrow. Former Members: Jason Badamo; Kenneth M. Boyd; Matthew Enos; Jenny Gallardo; Jacek Jarczynski; Ji Yun Lee; Mirjana McGrosky; Susan Morell; Angela Nguyen. Ann Nour; Meredith Sanchez; Kate Steinberg. Royal Victorian Eye & Ear Hospital, East Melbourne, Australia: Richard J. Stawell, MD (Director); Matthew Ayres; Gaurav Bhardwaj, MD; Lisa Breayley; Jessica Brennan; Thuy Chau; Xavier Fagan, MD; Lauren Hodgson; Maria Kolic; Lyndell Lim, MD; Ming-Lee Lin, MD; Cecilia Ling, MD; Julie Morrison (Ewing); Andrew Newton; Carly Parfett, MPH; Dania Qatarneh, MD; Sutha Sanmugasundram; Richard Smallwood; Robyn Troutbeck, MD; Ehud Zamir, MD. Former Members: Carly D’Sylva; Elizabeth Glatz; Nicola Hunt; Lisa Jones; Ignatios Koukouras; Rachel McIntosh; Suzanne Williams. Rush University Medical Center, Chicago, IL: Pauline T. Merrill, MD (Director); Danielle Carns; Cierra Foster; Marina Gilca, MD; George Parlitsis, MD; Eileen Tonner, CC, VA, DS; Denise L. Voskuil-Marre, BS; Kisung Woo. Former Members: Bruce Gaynes; Christina Giannoulis; Pam Hulvey; Elaine Kernbauer; Heena S. Khan, BA; Sarah J. Levine; Len Richine; Barbara Tazioli; Scott Toennessen. Texas Retina Associates, Dallas, TX: Robert C. Wang, MD (Director); Sally Arceneaux; Daniel Carpintero, BA; Karen Duignan; Gary E. Fish, MD; Bernice Ford; Nicholas Hesse; Diana Jaramillo; Michael Mackens; Brenda Sanchez; Tina Stanley. Former Members: Hank Aguado; Jean Arnwine; David Callanan, MD; Kimberly Cummings; Keith Gray; Susie Howden; Karin Mutz; Brenda Sanchez. United Kingdom Institute of Ophthalmology, London, UK: Susan Lightman, MD, PhD (Director); Lyndon DaCruz, MD; Rose Gilbert, MBBS, MRCOphth; Filis Ismetova, MD; Alexa King; Aziza Mirza; Ashley Prytherch; Iazha Talat, MD; Sophie Seguin-Greenstein; Oren Tomkins-Netzer; Sophia Zagora, MD;. Former Members: Asat Bar; Kate Edwards; Lavanish Joshi; Jiten Moraji; Ahmed Samy, MD; Timothy Stubbs; Simon Taylor, MD; Hamish Towler; Rebecca Tronnberg. University of California at Los Angeles, Los Angeles, CA: Gary N. Holland, MD (Director); Robert D. Almanzor, COA; Meghan Berkenstock, MD; Christian Boeni, MD; Jose Castellanos, COT; Orly Catz; Jeff Craddock; Lauren Eash; Serina Gonzales; Jonathan Heston; Jean Pierre Hubschman, MD; Olivia Lee, MD; Ralph D. Levinson, MD; Colin A. McCannel, MD; Rosio Mendoza; Renato Obispo; Daniel Raygoza; Jasmine Tam. Former Members: Rose Gilbert; Christine R. Gonzales, MD; Anurag Gupta, MD; Ann K. Johiro, NP; Partho S. Kalyani, MD; Michael A. Kapamajian, MD; Peter J. Kappel, MD; Alla Kukuyev, MD; Racheal Niederer; Efthymia Pavlidou; Susan S. Ransome, MD.



University of California at San Diego, San Diego, CA: Former Members: Cheryl Arcinue, MD (Director); Giulio Barteselli, MD; Janne Chuang; Tom Clark, BSc, CRA; Denine E. Cochran, COT, CCRC; Glenn Currie; William R. Freeman, MD; Joshua Hedaya, MD; Tiara Kemper; Igor Kozak, MD; Jacqueline M. LeMoine; Megan E. Loughran, BA; Luzandra Magana; Veronica Mendoza; Francesca Mojana, MD; Victoria Morrison, MD; Vivian Nguyen; Stephen F. Oster, MD; Debbie Powell, BBA. University of California at San Francisco, San Francisco, CA: Nisha Acharya, MD (Director); Erica Browne, MD; Thuy Doan, MD, PhD; John Gonzales, MD; Betty Hom; Shannon Khan; Mary Lew, BA; Sarah Lopez; Maya Rao, MPH; Jay Stewart, MD; Lina Zhong. Former Members: Debra Brown; David Clay; Claire M. Khouri, BA; Salena Lee, OD; Todd P. Margolis, MD; Ira G. Wong, MD University of Illinois at Chicago, Chicago, IL (currently Northwestern University): Debra A. Goldstein, MD (Director); Andrea Birnbaum, MD, PhD; Natalia Brooks; Gemma De la Rosa, COT; Carmen Ramirez; Lucious Robinson III; Evica Simjanowski, CRA. Former Members: Anna L. Castro-Malek, BA, CCRC; Catherine E. Crooke; Andrea Degillio, CRA; Melody Huntley; Katrina Nash; Marcia Niec; Dimitry Pyatetsky, MD; Misel Ramirez; Zuzanna Rozenbajgier, MS; Mariner Skelly, CRA; Howard H. Tessler, MD. University of Miami, Miami, FL: Janet L. Davis, MD (Director); Thomas A. Albini, MD; Marie Chin; Jim Crowell; Antonio Cubillas; Paula Dear; Giselle De Oliveira; Joseph Donahue; Donna Goertz; Rasec Fabregas; Marcella Hicky; Carmen Huerta; Jennifer Johnson; Michael Kicak; Christiaan Lopez Miro; Veronica Miranda; Daisy Monteagudo; Jim Oramas; Sira Padron; Denice Patino; Demetria Rahmings; Angelo Sablon; Stephen Schwartz, MD, MBA; Brandon Sparling; Richard R. Stanfield; Richard Vorperian; Angie White. Former Members: Daniela Castaño; Ariana Elizondo, BS, CCRP; Macy Ho; Jaclyn L. Kovach, MD; Richard C-S Lin, MD; Efrem Mandelcorn; Jackie K-D Nguyen, MD; Aura Pacini; Susan Pineda; David A. Pinto; Jose Rebimbas; Kimberly E. Stepien, MD; Claudia Teran. University of Michigan, Ann Arbor, MI: Susan G. Elner, MD (Director); Hillary Bernard; Rebecca Brown, COA; Linda Fournier, COT; Lindsay Godsey; Linda Goings; Moella Hesselgrave, COA; Munira Hussain; K. Thiran Jayasundera, MD; Robert Prusak; Laura Rozek; Anjali Shah, MD; Timothy Steffens, CRA; Pamela Titus, COT; Katie Weier, CRA. Former Members: Melissa Bergeron, COA; Reneé Blosser, COMT; Rebecca Brown, COA; Carrie Chrisman-McClure; Julie R. Gothrup, COA; Richard Hackel; Stephen J. Saxe, MD; Deanna Sizemore, COA. University of Pennsylvania, Philadelphia, PA: Benjamin Kim, MD (Director); Tomas Aleman, MD; Mauricio Alvarez; James Berger; Michael Bezzerides; Dominique Caggiano; Judy Chen; Cheryl Devine; Sheri Drossner, MSW; Joan C. DuPont; Andre Estanislau; Sheri Grend-Drossner, MSW; John H. Kempen, MD, PhD; Albert M. Maguire, MD; Sara Morales; Janice Petner; Collin Russell; Harpal Sandhu, MD; Beth Serpentine. Former Members: Stephanie Engelhard; Armin Faradaghi; Tim Hopkins, MD; Dawn McCall; Monique McRay; Daniel Will, MD; Wei Xu, Jonathan Lo, Rebecca Salvo, Elizabeth Windsor; Laurel Weeney. University of South Florida, Tampa, FL: Peter R. Pavan, MD (Director); Ken Albritton; Swetangi Bhaleeya, MD; Sharon Charton; JoAnn Leto; Brian Madow, MD; Paula Russian; Scott



E. Pautler, MD; Wyatt Saxon; Susan Scherouse. Former Members: Burton Goldstein, MD; Amy Klukoff; Lucy Lambright; Lori Mayor; Kim McDonald; Maria Ortiz; Susan Scymanky; Judy Soto; Dee Dee Szalay. University of Southern California, Los Angeles, CA: Narsing Rao, MD (Director); Daniel Barajas; Cullen Barnett, CRA, COT; Tamara Davis; Jackie Douglass; Cornelia Gottlieb;Yoon Hee Kim; Ryan Imagiire; Jay Jiang; Luis Lozano; Maria Mendoza; Patricia Rivias. Former Members: Alexia Aguirre; Lawrence Chong, MD; Lupe Cisneros, COA; Elizabeth Corona; Dean Eliott, MD; Amani Fawzi, MD; Jesse Garcia; Rahul Khurana, MD; Jennifer Lim, MD; Judith Linton; Rachel Mead; Margaret Padilla, CCRP; Sylvia Ramos; Julie H. Tsai, MD. University of Utah, Salt Lake City, UT: Albert Vitale, MD (Director); Susan Allman; Paul S. Bernstein, MD, PhD; Melissa Chandler; Katie Farnsworth, BS; Kelliann Farnsworth; James Gilman, CRA; Deborah Harrison, MS, CCRC; Paula Morris, CRA; Akbar Shakoor, MD; Becky Weeks, CRA; Kimberley Wegner, BS, CRC. Former Members: Bonnie Carlstrom, COA; Sandra Hanseen, COA; Diana Ramirez; Virginia Eye Consultants, Norfolk, VA: Former Members: John D. Sheppard, MD, MMSc (Director); Brianne Anthony; Amber Casper; R. Denise Cole; Nancy Crawford; Lisa Felix-Kent, COA; Jeanette Fernandez, COMT; Lisa Franklin; Krista Hamelin; Tari Johnson, BS; Jen Martin; Rebecca Marx; Stephen V. Scoper, MD. Gregory Schultz, DD; Joseph Webb, BS; Pamela Yeager. Vitreoretinal Consultants, Houston, TX (currently: Retina Consultants of Houston): Rosa Y. Kim, MD (Director); Belinda Almanza; Matthew S. Benz, MD; David M. Brown, MD; Eric Chen, MD; Marie Chin; Cassandra Cone; Richard H. Fish, MD; Christopher Henry, MD; Eric Kegley, BA, CRA, COA; Nubia Landaverde; James Major, Jr., MD; Ronan O’Malley, MD; Chelsey Moore; Stephanie Muñoz; Beau Richter; Amy Schefler, MD; Robert Smith; Veronica Sneed; Cary Stoever; Tien P. Wong, MD; Charles Wykoff, MD. Former Members: Rebecca De La Garza; Shayla Friday (Hay); Karin Mutz ; Laura Shawver, CCRP, COT. Washington University, St. Louis, MO: P. Kumar Rao, MD (Director); Eve Adcock; Patricia Arnold; Sarah Brown; Sarah Gould; John Greer, COT; Amanda Hebden; Humeyra Karacal, MD; Charla Meyer; Melanie Quinn; Amanda Penrod; Greg Rathert. Former Members: Amy Baladenski; Kevin J. Blinder, MD; Rhonda Curtis; Ashley Hartz; Jamie Kambarian; Pam Light; Rajendra S. Apte, MD, PhD; Sam Pistorius; Gaurav K. Shah, MD; Russell VanGelder, MD, PhD. Executive Committee: Douglas A. Jabs, MD, MBA (Chair); Michael M. Altaweel, MD; Sangeeta Bhargava, PhD; Donald Everett, PhD; Janet T. Holbrook, PhD, MPH; John H. Kempen, MD, PhD; Elizabeth Sugar, PhD. Steering Committee: Douglas A. Jabs, MD, MBA (Chair); Robert D. Almanzor, COA; Michael M. Altaweel; Diane Brown; James P. Dunn, MD; Janet T. Holbrook, PhD, MPH; Gary N. Holland, MD; John H. Kempen, MD, PhD; Rosa Y. Kim, MD; Nancy Prusakowski, MS; Jennifer E. Thorne, MD, PhD. Former Members: Stephen G. Bolton, RN, BSN; Lisa M. Brune, RN, BSN; Tom Clark, CRA; James Gilman; Larry Hubbard, MAT; Natalie Kurinij, PhD; Daniel F. Martin, MD; Robert B. Nussenblatt, MD.



Data, Safety and Monitoring Committee: Voting members: Janet Wittes, PhD (Chair); William E. Barlow, PhD; Alice T. Lyon, MD; Kim Overby, MD; Alan G. Palestine, MD; Lee S. Simon, MD. Non-voting members: Michael M. Altaweel, MD; Sangetta Bhargava, PhD; Donald Everett, PhD; Janet T. Holbrook, PhD, MPH; Douglas A. Jabs, MD, MBA. Former Members: Marc Hochberg, MD; Natalie Kurinij, PhD James T. Rosenbaum, MD; Harmon Smith, PhD. Surgical Quality Assurance Committee: John H. Kempen, MD, PhD (Chair); Glenn J. Jaffe, MD. Former Members: Janet Davis, MD; James P. Dunn, MD; Daniel F. Martin, MD; Jennifer Thorne, MD; Albert Vitale, MD. Medical Therapy Quality Assurance Committee: Jennifer E. Thorne, MD, PhD (Chair); Nisha R. Acharya, MD, MS; Douglas A. Jabs, MD, MBA; John H. Kempen, MD, PhD; Paul A. Latkany, MD; Albert T. Vitale, MD. Former Members: Robert B. Nussenblatt, MD, MPH; Russell VanGelder, MD, PhD. Visual Function Quality Assurance Committee: Robert D. Almanzor, COA (Chair); Jeffrey A. Boring, COA; Deborah Gibbs, COMT, CCRC; Salena Lee, OD, FAAO; Nancy Prusakowski; Jennifer E. Thorne, MD, PhD (Advisor). Former Members: Judith Alexander, BA, CCRP; Wai Ping Ng, BS. Glaucoma Committee: David S. Friedman, MD (Chair); Anna Adler, MS; Judith Alexander, BA, CCRP; Alyce Burke, MPH; Janet T. Holbrook, PhD, MPH; Joanne Katz, ScD; John H. Kempen, MD, PhD; Nancy Prusakowski, MS; Susan Reed, BS; Jennifer E. Thorne, MD, PhD; Husam Ansari, MD, PhD (consultant). Former Members: Nicholas Cohen, MS; Sanjukta Modak, MS; Wai Ping Ng, BS. Statistical Analysis Committee: Elizabeth A. Sugar, PhD (Chair); Alyce E. Burke, MPH; Janet T. Holbrook, PhD, MPH; Mark L. Van Natta, MHS. Former Members: Lea T. Drye, PhD; Kevin Frick, PhD; JoAnn Katz, ScD; Thomas A. Louis, PhD; Sanjukta Modak, MS; David Shade, JD. Chairman’s Office: Mount Sinai School of Medicine, New York, NY: Douglas A. Jabs, MD, MBA (Research Group Chairman); Karen Pascual, MBA; Jill S. Slutsky-Sanon, MPA. Former Members: Colby Glomp; Melissa A. Nieves, BA; Maria Stevens, CM, Amanda Allen; Yasmin Hilal, MHS. University of Pennsylvania: John H. Kempen, MD, PhD (Research Group Vice-Chairman and Protocol Chairman) Coordinating Center, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD: Janet T. Holbrook, PhD, MPH (Director); Francis Abreu, ScM; Alyce Burke, MPH; Cathleen Ewing; David S. Friedman, MD, PhD; Andrea Lears, BS; Jill Meinert; Vinnette Morrison, BS; Deborah Nowakowski; Nancy Prusakowski, MS; Dave M. Shade, JD; Jacqueline Smith, AA; Elizabeth A. Sugar, PhD; Jennifer E. Thorne, MD, PhD; Mark Van Natta, MHS. Former Members: Anna Adler, MS; Judith Alexander, BA; Jeff Boring, COA; Lea T. Drye, PhD; Kevin D. Frick, PhD; Rosetta Jackson; Christian Jimenez; Joanne Katz, ScD; Ariel Landers; Thomas A. Louis, PhD; Curtis L. Meinert, PhD; Sanjukta Modak, MS; Wai Ping Ng, BS; Girlie Reyes, BS; Weijiang Shen, MS; Karen Steuernagle; James A. Tonascia, PhD; Richard Zheng, MS.



University of Wisconsin Fundus Photograph Reading Center, Madison, WI: Michael M. Altaweel, MD (Director); Nathan Diers; Amitha Domalpally, MD; Anne Goulding; Daniel Lawrence, PhD; Jeong Won Pak, PhD; Susan Reed, BS; Pam Vargo; Hugh Wabers. Former Members: James Allan, BSc; Wendy K. Benz, PhD; Debra J. Christianson, BS; Geoffrey Chambers, MS; Margaret A. Fleischli, AB, DVM; Jacquelyn Freund, MS; Vonnie Gama; Sapna Gangaputra, MD, MPH; Kathleen E. Glander, BBA; Anne Goulding, BA; Dennis Hafford; Susan E. Harris, MS; Larry D. Hubbard, MAT; Kristine A. Johnson; Jeffrey M. Joyce, MS; Christina N. Kruse, BA; Dawn J. Myers, BS; Lauren Nagle; Gwyn E. Padden-Lechten, BS; Alyson Pohlman, BA; James L. Reimers, BA; Amy Remm, BS; Ruth A. Shaw, BS; Peggy Sivesind; Dennis Thayer; Erika Treichel, DVM; Kelly J. Warren, RN, BS, MSES; Sheila M. Watson, BS, DVM; Mary K. Webster, BS; James K. White, BME; Tara Wilhelmson, BS; Grace Zhang, BA.



eTable 1. Incident Ocular and Systemic Adverse Outcomes for Eyes/Patients Utilizing Assigned Therapy. Risk of these outcomes during the first seven years of follow-up among those at risk at baseline. Analysis includes those that initiated the assigned treatment (implant or systemic) within 6 months of randomization. Follow-up for those that were assigned systemic therapy was censored on the date of implantation.

Ocular outcomes Cumulative % with event within 7 years, (95% CI)*

Hazard Ratio (95% CI)

P-value

Eyes with an event/at

risk†

Implant Eyes with an event/

at risk†

Systemic (No Implant Use)

Implant/ Systemic

Glaucoma and IOP events IOP ≥ 30 mmHg 87/187 47.6%

(38.9%, 55.0%) 14 / 221

7.0% (2.8%, 11.0%)

8.57 (4.75, 15.5)

< 0.001

IOP ≥ 24 mmHg 129/187 69.7% (61.0%, 76.5%)

44 / 220

21.3% (14.0%, 28.0%)

4.77 (3.13, 7.25)

< 0.001

IOP ≥ 10 mmHg increase from baseline

128/187 69.0% (59.9%, 76.1%)

39 / 222

19.3% (12.7%, 25.5%)

5.45 (3.61, 8.20)

< 0.001

Glaucoma‡ 71/178 40.5% (31.1%, 48.7%)

16 / 208

9.3% (3.3%, 14.9%)

5.46 (2.96, 10.1)

< 0.001

Use of IOP-lowering therapy (medicine, surgery)

126/158 81.4% (72.0%, 87.6%)

53 / 194

28.3% (19.0%, 36.6%)

4.93 (3.29, 7.38)

< 0.001

IOP-lowering surgery§ 85/173 49.6% (40.3%, 57.5%)

8 / 207

5.1% (1.0%, 9.0%)

Before 2 years 55/173 32.0% (22.7%, 40.1%)

2 / 207

1.1% (0.0%, 2.5%)

36.2 (8.73, 150)

< 0.001

2 years or later (among those at risk at 2 years)

30/112 30.7% (19.4%, 40.3%)

6 / 176

4.1% (0.2%, 7.8%)

8.18 (3.07, 21.8)

<0.001

Cataract events Incident cataract 43/43 98.5%

(95.3%, 99.5%) 38 / 49

79.5% (59.6%, 89.7%)

5.95 (3.04, 11.6)

<0.001

Cataract surgery 107/109 99.5% (98.0%, 99.9%)

43 / 121

42.1% (28.4%, 53.1%)

9.39 (5.52, 16.0)

< 0.001

Potential complications of implant



surgery IOP ≤ 6 mmHg (hypotony) 49/180 24.8%

(17.0%, 31.8%) 21 / 210

11.4% (5.8%, 16.6%)

2.53 (1.39, 4.61)

0.002

Vitreous hemorrhage§ 42/188 21.6% (14.7%, 27.9%)

8 / 222

4.2% (1.0%, 7.3%)

Before 2 years 38/188 19.1% (12.6%, 25.1%)

5 / 222

2.4% (0.0%, 4.9%)

9.16 (3.08, 27.2)

< 0.001

2 years or later (among those at risk at 2 years)

6/147 5.2% (1.0%, 9.2%)

3 / 190

1.8% (0.0%, 3.9%)

2.14 (0.55, 8.26)

0.27



eTable 1. Incident Ocular and Systemic Adverse Outcomes for Eyes/Patients Utilizing Assigned Therapy. Risk of these outcomes during the first seven years of follow-up among those at risk at baseline. Analysis includes those that initiated the assigned treatment (implant or systemic) within 6 months of randomization. Follow-up for those that were assigned systemic therapy was censored on the date of implantation. (continued)

Systemic outcomes Cumulative % with event within 7 years

(95% CI)* Hazard Ratio (95%

CI) P-value

Patients with an event/ at risk†

Implant Patients with an event/ at risk†

Systemic (No Implant Use)

Implant/ Systemic

Hyperlipidemia diagnosis requiring treatment

7/87 6.2% (0.7%, 11.5%)

9/ 85

12.6% (4.4%, 20.1%)

0.62 (0.23, 1.67)

0.34

Hypertension diagnosis requiring treatment 11/85 10.0% (3.1%, 16.4%)

14 / 84

16.9% (7.6%, 25.2%)

0.62 (0.28, 1.38)

0.24

Diabetes mellitus 5/102 4.3% (0.0007%, 8.4%)

7 / 109

8.1% (2.0%, 13.8%)

0.63 (0.19, 1.99)

0.43

Osteopenia 19/55 41.8% (23.1%, 55.9%)

20 / 60

55.6% (30.1%, 71.8%)

0.90 (0.47, 1.69)

0.74

Osteoporosis 6/108 5.9% (1.1%, 10.4%)

8 / 97

8.9% (2.2%, 15.2%)

0.60 (0.20, 1.73)

0.34

Fractures 16/122 11.4% (5.3%, 17.2%)

17 / 119

17.2% (8.9%, 24.7%)

0.73 (0.36, 1.46)

0.37

Hospitalization 57/122 47.2% (36.9%, 55.9%)

51 / 119

45.7% (34.4%, 55.1%)

0.87 (0.59, 1.28)

0.48

Infection requiring treatment 68/122 56.6% (46.5%, 64.9%)

77 / 119

73.1% (62.4%, 80.8%)

0.65 (0.46, 0.90)

0.009

White blood cell counts ≤ 2500 cells/µL** 1/120 0.8% (0.0%, 2.5%)

5 / 106

4.1% (0.06%, 8.0%)

0.16 (0.01, 1.41)

0.10

Platelet count ≤ 100,000//µL** 6/118 5.5% (1.1%, 9.7%)

2 / 105

1.2% (0.0%, 3.6%)

2.50 (0.50, 12.37)

0.26

Hemoglobin ≤ 10g/dL** 2/120 1.7% (0.0%, 4.1%)

4 / 104

2.4% (0.0%, 5.7%)

0.38 (0.06, 2.06)

0.26

Hepatotoxicity**†† 6/116 5.3% (1.0%, 9.4%)

4 / 103

3.9% (0.0%, 8.1%)

1.27 (0.35, 4.51)

0.71

Nephrotoxicity**‡‡ 9/116 8.0% (2.8%, 12.9%)

6 / 105

6.5% (1.3%, 11.4%)

1.30 (0.46, 3.65)

0.62

Cancer§§ 2/122 2.0% (0.0%, 4.6%)

2 / 120

1.0% (0.0%, 2.9%)

0.77 (0.10, 5.45)

0.79

Death 3/122 1.7% (0.0%, 4.0%)

4 / 120

2.1% (0.0%, 5.0%)

0.58 (0.12, 2.59)

0.47



Data are from the Multicenter Uveitis Steroid Treatment (MUST) Trial and Follow-up Study. CI = confidence interval; IOP = intraocular pressure. *Calculated using Kaplan-Meier model; percentages will not exactly equal those that would be obtained using raw counts. †Excludes those with prevalent complications or missing data at baseline. ‡Measured yearly. §The test of interaction p-values for the change in HR before versus after 2 years was p = 0.078 for IOP surgery and 0.085 for vitreous hemorrhage. **Measured annually. ††Aspartate aminotransferase or alanine aminotransferase greater than twice the upper limit of normal. ‡‡Creatinine > 1.5 mg/dl or discontinuation of an immunosuppressive drug stopped because of renal toxicity. §§Excludes all non-melanoma skin cancers.



eTable 2. Quality of Life Outcomes for Participants Randomized to Implant or Systemic Therapy. Results are summarized for the seven years of follow-up from baseline. Higher scores indicate better quality of life.

Visit Estimates within Each Treatment

Group Mean (95% CI)

Change from BL within Each Treatment Group

Mean (95% CI)

Difference in Change from

BL† Mean (95% CI)

P-value

N* Implant N* Systemic Implant Systemic Implant-Systemic Vision-related QoL** VFQ-25 (Overall Composite), MCID: 4-6 points1 Baseline 129 58.4

(54.7, 62.2) 126 62.6

(59, 66.3)

1-year 129 70.6 (66.6, 74.5)

115 67.5 (63.9, 71.2)

12.1 (8.9, 15.3)

4.9 (2.1, 7.7)

7.2 (3.0, 11.4)

< 0.001

2-years 232 69.8 (65.9, 73.8)

114 69.4 (65.5, 73.3)

11.4 (8.1, 14.7)

6.7 (3.6, 9.9)

4.7 (0.1, 9.2)

0.04

3-years 118 70.4 (66.3, 74.4)

107 71.7 (67.9, 75.6)

11.9 (8.6, 15.2)

9.1 (5.8, 12.4)

2.8 (-1.8, 7.5)

0.23

4-years 111 67.6 (63.6, 71.7)

100 71.0 (67.0, 74.9)

9.2 (6.3, 12.2)

8.3 (4.7, 11.9)

0.9 (-3.8, 5.5)

0.71

5-years 108 65.5 (61.2, 69.8)

99 71.6 (67.6, 75.6)

7.1 (3.5, 10.6)

9.0 (5.4, 12.5)

-1.9 (-6.9, 3.1)

0.45

6-years 93 64.6 (60.2, 69)

96 70.7 (66.7, 74.6)

6.1 (2.7, 9.6)

8.0 (4.4, 11.6)

-1.9 (-6.9, 3.2)

0.46

7-years 90 63.1 (58.6, 67.5)

89 68.3 (64.1, 72.6)

4.6 (1.2, 8.1)

5.7 (1.9, 9.5)

-1.0 (-6.1, 4.0)

0.68

Health Utility**

EuroQol EQ-5D Health Utility Index, MCID: 0.06-0.07 points2 Baseline 129 0.81

(0.77, 0.84) 125 0.82

(0.79, 0.85)

1-year 120 0.82 (0.79, 0.86)

115 0.79 (0.76, 0.83)

0.02 (-0.02, 0.05)

-0.03 (-0.07, 0.01)

0.05 (0.001, 0.10)

0.04

2-years 118 0.83 (0.79, 0.86)

114 0.80 (0.77, 0.84)

0.02 (-0.01, 0.06)

-0.02 (-0.05, 0.02)

0.04 (-0.01, 0.09)

0.07

3-years 112 0.82 (0.79, 0.86)

104 0.81 (0.77, 0.84)

0.02 (-0.02, 0.06)

-0.02 (-0.05, 0.02)

0.03 (-0.02, 0.09)

0.14

4-years 106 0.84 (0.80, 0.87)

101 0.80 (0.76, 0.84)

0.03 (0, 0.06)

-0.02 (-0.06, 0.02)

0.05 (0.005, 0.10)

0.03

5-years 99 0.81 (0.77, 0.84)

98 0.81 (0.77, 0.84)

-0.0004 (-0.03, 0.03)

-0.01 (-0.05, 0.02)

0.01 (-0.03, 0.06)

0.52

6-years 93 0.79 (0.75, 0.83)

96 0.79 (0.75, 0.83)

-0.01 (-0.05, 0.02)

-0.03 (-0.08, 0.01)

0.02 (-0.04, 0.08)

0.46

7-years 89 0.80 (0.77, 0.83)

88 0.77 (0.72, 0.81)

-0.01 (-0.04, 0.03)

-0.06 (-0.1, -0.01)

0.05 (-0.01, 0.11)

0.06



eTable 2. Quality of Life Outcomes for Participants Randomized to Implant or Systemic Therapy. Results are summarized for the seven years of follow-up from baseline. Higher scores indicate better quality of life. (continued)

Visit Estimates within Each Treatment Group Mean (95% CI)

Change from BL within Each Treatment Group

Mean (95% CI)

Difference in Change from

BL† Mean (95% CI)

P-value

N* Implant N* Systemic Implant Systemic Implant-Systemic

Generic health-related QoL** SF-36: Physical Health Component, MCID: 3-5 points3 Baseline 129 46.7

(44.9, 48.5) 126 48.6

(46.9, 50.4)

1-year 120 47.7 (45.8, 49.7)

114 46.7 (44.9, 48.6)

1.1 (-0.5, 2.6)

-1.9 (-3.6, -0.2)

2.96 (0.67, 5.25)

0.01

2-years 118 47.8 (45.8, 49.8)

114 46.9 (44.9, 48.8)

1.1 (-0.6, 2.8)

-1.8 (-3.6, 0)

2.87 (0.47, 5.27)

0.02

3-years 110 47.8 (45.9, 49.7)

107 47.2 (45.3, 49.1)

1.1 (-0.6, 2.8)

-1.4 (-3.3, 0.4)

2.52 (0.05, 4.98)

0.05

4-years 107 47.1 (45.1, 49)

100 47.4 (45.5, 49.2)

0.4 (-1.2, 1.9)

-1.3 (-3.2, 0.6)

1.64 (-0.75, 4.03)

0.18

5-years 99 46.5 (44.6, 48.5)

98 47.0 (45.1, 48.9)

-0.2 (-2, 1.6)

-1.6 (-3.4, 0.2)

1.47 (-1.00, 3.94)

0.24

6-years 93 47 (45.1, 48.9)

95 47.5 (45.2, 49.7)

0.3 (-1.4, 2)

-1.2 (-3.4, 1.00)

1.45 (-1.27, 4.17)

0.29

7-years 89 45.2 (43.3, 47.2)

88 45.3 (42.9, 47.8)

-1.5 (-3.1, 0.2)

-3.3 (-5.6, -0.9)

1.82 (-1.00, 4.63)

0.21

SF-36: Mental Health Component, MCID: 3-5 points3 Baseline 129 47.1

(44.9, 49.4) 126 48.0

(45.9, 50)

1-year 120 50.6 (48.7, 52.6)

114 46.2 (43.8, 48.7)

3.5 (1.4, 5.6)

-1.7 (-3.9, 0.5)

5.23 (2.24, 8.22)

< 0.001

2-years 118 49.6 (47.5, 51.6)

114 46.9 (44.6, 49.3)

2.4 (0.2, 4.6)

-1.0 (-3.3, 1.3)

3.46 (0.35, 6.58)

0.03

3-years 110 49.9 (47.8, 51.9)

107 47.9 (45.7, 50.1)

2.7 (0.6, 4.8)

-0.03 (-2.1, 2.1)

2.75 (-0.18, 5.69)

0.07

4-years 107 48.9 (46.7, 51)

100 48.7 (46.6, 50.9)

1.7 (-0.6, 4)

0.8 (-1.6, 3.2)

0.95 (-2.30, 4.19)

0.57

5-years 99 48.0 (45.8, 50.3)

98 49.4 (47.2, 51.6)

0.9 (-1.2, 3)

1.5 (-0.9, 3.9)

-0.59 (-3.73, 2.54)

0.71

6-years 93 49.1 (47.0, 51.3)

95 47.8 (45.4, 50.2)

2.0 (-0.4, 4.4)

-0.1 (-2.9, 2.6)

2.12 (-1.44, 5.69)

0.24

7-years 89 49.8 (47.5, 52)

88 46.3 (43.8, 48.8)

2.6 (0.1, 5.2)

-1.6 (-4.3, 1.0)

4.28 (0.65, 7.91)

0.02

Data are from the Multicenter Uveitis Steroid Treatment (MUST) Trial and Follow-up Study. *N is the sample size at each visit for each treatment group. † Positive values favor the implant. ** QoL=Quality of Life; MCID=Minimal Clinically Important Difference. For Vision-Related QoL, the potential range of values is 0 to 100; the observed range of values was 2.27 to 100. For EuroQol EQ-5D health utility, the range of possible values is from -0.11 to 1.00; the observed range of values was -0.038 to 1.00. For the SF-36 Physical and Mental Health Components the range of possible values is each from 0 to 100; the observed range of values was 12.49 to 73.98 and 0.20 to 71.15, respectively.



eTable 2. Quality of Life Outcomes for Participants Randomized to Implant or Systemic Therapy. Results are summarized for the seven years of follow-up from baseline. Higher scores indicate better quality of life. (continued) References: 1. Suner IJ, Kokame GT, Yu E, Ward J, Dolan C, Bressler NM. Responsiveness of NEI VFQ-25 to

changes in visual acuity in neovascular AMD: validation studies from two phase 3 clinical trials. Invest Ophthalmol.Vis.Sci. 8/2009 2009;50(8):3629-3635.

2. Pickard AS, Neary MP, Cella D. Estimation of minimally important differences in EQ-5D utility

and VAS scores in cancer. Health Qual.Life Outcomes. 2007 2007;5:70. 3. Hays RD, Morales LS. The RAND-36 measure of health-related quality of life. Ann.Med. 7/2001

2001;33(5):350-357.



eFigure 1. Treatment Patterns for Eyes With Uveitis Assigned to (a) Implant or (b) Systemic Therapy. Treatment use at each six-month visit during the first seven years of follow-up is summarized. Implant=fluocinolone acetonide 0.59 mg implant; Activity=clinician-determined status of intraocular inflammation as active (as opposed to inactive/suppressed). Comparable medication is defined as placement of an implant within 3 years or use of systemic therapy, or peri- or intraocular corticosteroid depot injections (e.g. triamcinolone acetonide depot, Ozurdex®) within the last six months. Individuals are classified into 4 mutually exclusive categories: on comparable medication with an implant (dark blue) or without an implant (light blue) or not on comparable medication with activity (gold) or without activity (green; possibly in remission). At 7 years, the percent of individuals in each group respectively was 27%, 30%, 7%, and 36% and for the implant group and 7%, 64%, 2%, and 27% for the systemic group, for those on comparable medication with an implant or without an implant or not on comparable medication with activity or without activity. [Data are from the Multicenter Uveitis Steroid Treatment (MUST) Trial and Follow-up Study.] (a)



Supplemental Materials for Intraocular vs. Systemic Therapy for Uveitis eFigures eFigure 1. Treatment Patterns for Eyes With Uveitis Assigned to (a) Implant or (b) Systemic Therapy. Treatment use at each six-month visit during the first seven years of follow-up is summarized. Implant=fluocinolone acetonide 0.59 mg implant; Activity=clinician-determined status of intraocular inflammation as active (as opposed to inactive/suppressed). Comparable medication is defined as placement of an implant within 3 years or use of systemic therapy, or peri- or intraocular corticosteroid depot injections (e.g. triamcinolone acetonide depot, Ozurdex®) within the last six months. Individuals are classified into 4 mutually exclusive categories: on comparable medication with an implant (dark blue) or without an implant (light blue) or not on comparable medication with activity (gold) or without activity (green; possibly in remission). At 7 years, the percent of individuals in each group respectively was 27%, 30%, 7%, and 36% and for the implant group and 7%, 64%, 2%, and 27% for the systemic group, for those on comparable medication with an implant or without an implant or not on comparable medication with activity or without activity. [Data are from the Multicenter Uveitis Steroid Treatment (MUST) Trial and Follow-up Study.] (continued) (b)



Supplemental Materials for Intraocular vs. Systemic Therapy for Uveitis eFigures eFigure 2. Distributions of (a) Weight and (b) Change in Weight From Randomization for Participants by Treatment Assignment. Weight results during the first seven years of follow-up for patients with uveitis assigned to implant and systemic therapy are shown in white and grey respectively. The middle line of each box represents the median and the ends of the boxes represent the inter-quartile range (IQR). The whiskers cover the shorter of 1.5 times the IQR or the interval to the maximal or minimal value. For the change in weight from randomization, the maximal range for the box-plot is +/- 25. The number of individuals next to the outlier symbols at 25 and -25 represent the number of individuals with a change greater than 25 in each direction. [Data are from the Multicenter Uveitis Steroid Treatment (MUST) Trial and Follow-up Study.] (a)



Supplemental Materials for Intraocular vs. Systemic Therapy for Uveitis eFigures eFigure 2. Distributions of (a) Weight and (b) Change in Weight From Randomization for Participants by Treatment Assignment. Weight results during the first seven years of follow-up for patients with uveitis assigned to implant and systemic therapy are shown in white and grey respectively. The middle line of each box represents the median and the ends of the boxes represent the inter-quartile range (IQR). The whiskers cover the shorter of 1.5 times the IQR or the interval to the maximal or minimal value. For the change in weight from randomization, the maximal range for the box-plot is +/- 25. The number of individuals next to the outlier symbols at 25 and -25 represent the number of individuals with a change greater than 25 in each direction. [Data are from the Multicenter Uveitis Steroid Treatment (MUST) Trial and Follow-up Study.] (continued) (b)



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