John H Kempen1, Michael M Altaweel2, Janet T Holbrook3, Elizabeth A Sugar4, Jennifer E Thorne5, Douglas A Jabs6. 1. Department of Ophthalmology, Massachusetts Eye and Ear, Boston3The Discovery Eye Center, MyungSung Christian Medical Center and MyungSung Medical School, Addis Ababa, Ethiopia. 2. Fundus Photograph Reading Center, Department of Ophthalmology and Visual Sciences, University of Wisconsin School of Medicine and Public Health, Madison. 3. Center for Clinical Trials and Evidence Synthesis, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland6Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland. 4. Center for Clinical Trials and Evidence Synthesis, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland7Department Biostatistics, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland. 5. Center for Clinical Trials and Evidence Synthesis, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland6Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland8Department of Ophthalmology, Johns Hopkins University School of Medicine, Baltimore, Maryland. 6. Center for Clinical Trials and Evidence Synthesis, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland6Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland9Department of Ophthalmology, Icahn School of Medicine at Mount Sinai, New York, New York10Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York.
Abstract
IMPORTANCE: A randomized clinical trial comparing fluocinolone acetonide implant vs systemic corticosteroids and immunosuppression for treatment of severe noninfectious intermediate, posterior, and panuveitides did not result in a significant difference in visual acuity at 2 and 4.5 years; longer-term outcomes are not known. OBJECTIVE: To compare the association between intravitreous fluocinolone acetonide implant vs systemic therapy and long-term visual and other outcomes in patients with uveitis. DESIGN, SETTING, AND PARTICIPANTS: Nonprespecified 7-year observational follow-up of the Multicenter Uveitis Steroid Treatment (MUST) randomized clinical trial comparing the alternative treatments. Follow-up was conducted in tertiary uveitis subspecialty practices in the United States (21), the United Kingdom (1), and Australia (1). Of 255 patients 13 years or older with intermediate, posterior, or panuveitis (active within ≤60 days) enrolled in the MUST trial between December 6, 2005, and December 9, 2008, 215 consented to ongoing follow-up through at least 7 years postrandomization (last visit, February 10, 2016). INTERVENTIONS: Participants had been randomized to receive a surgically placed intravitreous fluocinolone acetonide implant or systemic corticosteroids supplemented by immunosuppression. When both eyes required treatment, both eyes were treated. MAIN OUTCOMES AND MEASURES: Primary outcome was change from baseline in best-corrected visual acuity in uveitic eyes (5 letters = 1 visual acuity chart line; potential range of change in letters read, -121 to +101; minimal clinically important difference, 7 letters), analyzed by treatment assignment accounting for nonindependence of eyes when patients had 2 uveitic eyes. Secondary outcomes included potential systemic toxicities of corticosteroid and immunosuppressive therapy and death. RESULTS: Seven-year data were obtained for 161 uveitic eyes (70% of 90 patients assigned to implant) and 167 uveitic eyes (71% of 90 patients assigned to systemic therapy) (77% female; median age at enrollment, 48 [interquartile range, 36-56] years). Change in mean visual acuity from baseline (implant, 61.7; systemic therapy, 65.0) through 7 years (implant, 55.8; systemic therapy, 66.2) favored systemic therapy by 7.2 (95% CI, 2.1-12) letters. Among protocol-specified, prospectively collected systemic adverse outcomes, the cumulative 7-year incidence in the implant and systemic therapy groups, respectively, was less than 10%, with the exceptions of hyperlipidemia (6.1% vs 11.2%), hypertension (9.8% vs 18.4%), osteopenia (41.5% vs 43.1%), fractures (11.3% vs 18.6%), hospitalization (47.6% vs 42.3%), and antibiotic-treated infection (57.4% vs 72.3%). CONCLUSIONS AND RELEVANCE: In 7-year extended follow-up of a randomized trial of patients with severe intermediate, posterior, or panuveitis, those randomized to receive systemic therapy had better visual acuity than those randomized to receive intravitreous fluocinolone acetonide implants. Study interpretation is limited by loss to follow-up. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00132691.
IMPORTANCE: A randomized clinical trial comparing fluocinolone acetonide implant vs systemic corticosteroids and immunosuppression for treatment of severe noninfectious intermediate, posterior, and panuveitides did not result in a significant difference in visual acuity at 2 and 4.5 years; longer-term outcomes are not known. OBJECTIVE: To compare the association between intravitreous fluocinolone acetonide implant vs systemic therapy and long-term visual and other outcomes in patients with uveitis. DESIGN, SETTING, AND PARTICIPANTS: Nonprespecified 7-year observational follow-up of the Multicenter Uveitis Steroid Treatment (MUST) randomized clinical trial comparing the alternative treatments. Follow-up was conducted in tertiary uveitis subspecialty practices in the United States (21), the United Kingdom (1), and Australia (1). Of 255 patients 13 years or older with intermediate, posterior, or panuveitis (active within ≤60 days) enrolled in the MUST trial between December 6, 2005, and December 9, 2008, 215 consented to ongoing follow-up through at least 7 years postrandomization (last visit, February 10, 2016). INTERVENTIONS: Participants had been randomized to receive a surgically placed intravitreous fluocinolone acetonide implant or systemic corticosteroids supplemented by immunosuppression. When both eyes required treatment, both eyes were treated. MAIN OUTCOMES AND MEASURES: Primary outcome was change from baseline in best-corrected visual acuity in uveitic eyes (5 letters = 1 visual acuity chart line; potential range of change in letters read, -121 to +101; minimal clinically important difference, 7 letters), analyzed by treatment assignment accounting for nonindependence of eyes when patients had 2 uveitic eyes. Secondary outcomes included potential systemic toxicities of corticosteroid and immunosuppressive therapy and death. RESULTS: Seven-year data were obtained for 161 uveitic eyes (70% of 90 patients assigned to implant) and 167 uveitic eyes (71% of 90 patients assigned to systemic therapy) (77% female; median age at enrollment, 48 [interquartile range, 36-56] years). Change in mean visual acuity from baseline (implant, 61.7; systemic therapy, 65.0) through 7 years (implant, 55.8; systemic therapy, 66.2) favored systemic therapy by 7.2 (95% CI, 2.1-12) letters. Among protocol-specified, prospectively collected systemic adverse outcomes, the cumulative 7-year incidence in the implant and systemic therapy groups, respectively, was less than 10%, with the exceptions of hyperlipidemia (6.1% vs 11.2%), hypertension (9.8% vs 18.4%), osteopenia (41.5% vs 43.1%), fractures (11.3% vs 18.6%), hospitalization (47.6% vs 42.3%), and antibiotic-treated infection (57.4% vs 72.3%). CONCLUSIONS AND RELEVANCE: In 7-year extended follow-up of a randomized trial of patients with severe intermediate, posterior, or panuveitis, those randomized to receive systemic therapy had better visual acuity than those randomized to receive intravitreous fluocinolone acetonide implants. Study interpretation is limited by loss to follow-up. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00132691.
Authors: D A Jabs; J T Rosenbaum; C S Foster; G N Holland; G J Jaffe; J S Louie; R B Nussenblatt; E R Stiehm; H Tessler; R N Van Gelder; S M Whitcup; D Yocum Journal: Am J Ophthalmol Date: 2000-10 Impact factor: 5.258
Authors: H Nida Sen; Lea T Drye; Debra A Goldstein; Theresa A Larson; Pauline T Merrill; Peter R Pavan; John D Sheppard; Alyce Burke; Sunil K Srivastava; Douglas A Jabs Journal: Ocul Immunol Inflamm Date: 2012-04 Impact factor: 3.070
Authors: John H Kempen; Michael M Altaweel; Lea T Drye; Janet T Holbrook; Douglas A Jabs; Elizabeth A Sugar; Jennifer E Thorne Journal: Ophthalmology Date: 2015-08-20 Impact factor: 12.079
Authors: Sapna S Gangaputra; Craig W Newcomb; Marshall M Joffe; Kurt Dreger; Hosne Begum; Pichaporn Artornsombudh; Siddharth S Pujari; Ebenezer Daniel; H Nida Sen; Eric B Suhler; Jennifer E Thorne; Nirali P Bhatt; C Stephen Foster; Douglas A Jabs; Robert B Nussenblatt; James T Rosenbaum; Grace A Levy-Clarke; John H Kempen Journal: Am J Ophthalmol Date: 2019-07-22 Impact factor: 5.258
Authors: Caroline L Minkus; Maxwell Pistilli; Kurt A Dreger; Tonetta D Fitzgerald; Abhishek R Payal; Hosne Begum; R Oktay Kaçmaz; Douglas A Jabs; Robert B Nussenblatt; James T Rosenbaum; Grace A Levy-Clarke; H Nida Sen; Eric B Suhler; Jennifer E Thorne; Nirali P Bhatt; C Stephen Foster; Jeanine M Buchanich; John H Kempen Journal: Am J Ophthalmol Date: 2021-03-10 Impact factor: 5.488
Authors: Lucia Sobrin; Yinxi Yu; Samuel Han; Gayatri Susarla; John H Kempen; Rebecca A Hubbard; Brian L VanderBeek Journal: Ocul Immunol Inflamm Date: 2021-03-08 Impact factor: 3.728
Authors: Maxwell Pistilli; Marshall M Joffe; Sapna S Gangaputra; Siddharth S Pujari; Douglas A Jabs; Grace A Levy-Clarke; Robert B Nussenblatt; James T Rosenbaum; H Nida Sen; Eric B Suhler; Jennifer E Thorne; Nirali P Bhatt; C Stephen Foster; Hosne Begum; Tonetta D Fitzgerald; Kurt A Dreger; Michael M Altaweel; Janet T Holbrook; John H Kempen Journal: Ocul Immunol Inflamm Date: 2019-12-10 Impact factor: 3.728