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Qt2mh1j0hw.Pdf UCLA UCLA Previously Published Works Title Consensus on the Diagnosis and Management of Nonparaneoplastic Autoimmune Retinopathy Using a Modified Delphi Approach. Permalink https://escholarship.org/uc/item/2mh1j0hw Authors Fox, Austin R Gordon, Lynn K Heckenlively, John R et al. Publication Date 2016-08-01 DOI 10.1016/j.ajo.2016.05.013 Peer reviewed eScholarship.org Powered by the California Digital Library University of California Consensus on the Diagnosis and Management of Nonparaneoplastic Autoimmune Retinopathy Using a Modified Delphi Approach AUSTIN R. FOX, LYNN K. GORDON, JOHN R. HECKENLIVELY, JANET L. DAVIS, DEBRA A. GOLDSTEIN, CAREEN Y. LOWDER, ROBERT B. NUSSENBLATT, NICHOLAS J. BUTLER, MONICA DALAL, THIRAN JAYASUNDERA, WENDY M. SMITH, RICHARD W. LEE, GRAZYNA ADAMUS, CHI-CHAO CHAN, JOHN J. HOOKS, CATHERINE W. MORGANS, BARBARA DETRICK, AND H. NIDA SEN PURPOSE: To develop diagnostic criteria for nonpara- second-line treatments, though a consensus agreed that neoplastic autoimmune retinopathy (AIR) through biologics and intravenous immunoglobulin were consid- expert panel consensus and to examine treatment patterns ered appropriate in the treatment of nonparaneoplastic among clinical experts. AIR patients regardless of the stage of disease. Experts DESIGN: Modified Delphi process. agreed that more evidence is needed to treat nonparaneo- METHODS: A survey of uveitis specialists in the Amer- plastic AIR patients with long-term immunomodulatory ican Uveitis Society, a face-to-face meeting (AIR Work- therapy and that there is enough equipoise to justify ran- shop) held at the National Eye Institute, and 2 iterations domized, placebo-controlled trials to determine if nonpar- of expert panel surveys were used in a modified Delphi aneoplastic AIR patients should be treated with long-term process. The expert panel consisted of 17 experts, immunomodulatory therapy. Regarding antiretinal anti- including uveitis specialists and researchers with exper- body detection, consensus agreed that a standardized tise in antiretinal antibody detection. Supermajority assay system is needed to detect serum antiretinal anti- consensus was used and defined as 75% of experts in bodies. Consensus agreed that an ideal assay should agreement. have a 2-tier design and that Western blot and immuno- RESULTS: There was unanimous agreement among ex- histochemistry should be the methods used to identify perts regarding the categorization of autoimmune retinop- antiretinal antibodies. athies as nonparaneoplastic and paraneoplastic, including CONCLUSIONS: Consensus was achieved using a modi- cancer-associated retinopathy and melanoma-associated fied Delphi process to develop diagnostic criteria for retinopathy. Diagnostic criteria and tests essential to nonparaneoplastic AIR. There is enough equipoise to the diagnosis of nonparaneoplastic AIR and multiple sup- justify randomized, placebo-controlled trials to determine portive criteria reached consensus. For treatment, experts whether patients with nonparaneoplastic AIR should be agreed that corticosteroids and conventional immun- treated with long-term immunomodulatory therapy. Ef- osuppressives should be used (prescribed) as first- or forts to develop a standardized 2-tier assay system for the detection of antiretinal antibodies have been initiated as a result of this study. (Am J Ophthalmol 2016;168: Supplemental Material available at AJO.com. 183–190. Published by Elsevier Inc.) Accepted for publication May 12, 2016. From the Laboratory of Immunology, National Eye Institute, National Institutes of Health, Bethesda, Maryland (A.R.F., R.B.N., C.-C.C., J.J.H., H.N.S.); Stein Eye Institute, David Geffen School of Medicine at UTOIMMUNE RETINOPATHIES ARE A GROUP OF the University of California, Los Angeles, Los Angeles, California (L.K.G.); Kellogg Eye Center, University of Michigan, Ann Arbor, inflammatory-mediated diseases characterized by Michigan (J.R.H., T.J.); Bascom Palmer Eye Institute, University of the presence of antiretinal antibodies, visual field Miami Miller School of Medicine, Miami, Florida (J.L.D.); Department A deficits, and photoreceptor dysfunction in the setting of of Ophthalmology, Northwestern University Feinberg School of Medicine, Chicago, Illinois (D.A.G.); Cole Eye Institute, Cleveland progressive, otherwise unexplained vision loss. Autoim- Clinic, Cleveland, Ohio (C.Y.L.); Massachusetts Eye and Ear, Harvard mune retinopathies can be categorized as paraneoplastic Medical School, Boston, Massachusetts (N.J.B.); Veterans Affairs AIR (pAIR), which includes cancer-associated retinopathy Boston Healthcare System, Jamaica Plain, Massachusetts (N.J.B.); Department of Ophthalmology, George Washington University, (CAR) and melanoma-associated retinopathy (MAR), or Washington, DC (M.D.); Department of Ophthalmology, Mayo Clinic, nonparaneoplastic autoimmune retinopathy in the absence of Rochester, Minnesota (W.M.S.); Bristol Eye Hospital, University of malignancy. As autoimmune retinopathy (AIR) is the Bristol, Bristol, United Kingdom (R.W.L.); Ocular Immunology Laboratory, Casey Eye Institute (G.A.), and Department of Physiology preferred term for an acquired and presumed immune- & Pharmacology (C.W.M.), Oregon Health & Science University, mediated retinopathy due to antiretinal autoantibodies in Portland, Oregon; and Department of Pathology, Johns Hopkins the absence of a malignancy, we use AIR to indicate the University, School of Medicine, Baltimore, Maryland (B.D.). Inquiries to H. Nida Sen, 10 Center Drive 10D45, Bethesda, MD 20892- nonparaneoplastic form of autoimmune retinopathy unless 0001; e-mail: [email protected] otherwise indicated. 0002-9394/$36.00 PUBLISHED BY ELSEVIER INC. 183 http://dx.doi.org/10.1016/j.ajo.2016.05.013 Despite being described almost 20 years ago,1 AIR re- a structured communication method designed to elicit mains an ill-defined disease. The diagnosis of AIR is typi- and collate the opinions of experts through anonymity, cally made based on the presence of antiretinal controlled feedback, statistical group response, and multi- antibodies and a combination of certain clinical features, ple iterations.10,11 The Delphi method was first developed in the absence of another cause of symptoms. Although by the RAND Corporation in the 1950s to forecast the the prevalence of AIR is unknown, it is thought to be a impact of technology on warfare and has since been used rare entity. However, it is probable that AIR is more prev- throughout numerous healthcare fields including alent than thought and remains undiagnosed in many cases ophthalmology and in uveitis to build consensus among owing to the lack of standardized diagnostic criteria and its experts for the diagnosis and management of disease.10–15 protean clinical features that overlap with other retinal In diseases where clinical evidence is lacking, this degenerative diseases. Nonetheless, it is important to rule method is deemed suitable for the development of out malignant etiologies and treatable conditions when guidelines for diagnosis or management. The goal is to considering the diagnosis of AIR to prevent morbidity narrow the range of responses with each iteration to and treatable vision loss. arrive at an expert consensus. Ultimately, the Delphi While clinical features may vary considerably, process allows experts to work together in a structured commonly recognized manifestations have been identi- manner to gain a better understanding in areas where fied.2–5 The presence of circulating antiretinal antibodies consensus is lacking. is considered essential to the diagnosis of AIR. Although The modified Delphi process used in this study consisted great strides have been made in the detection and of multiple rounds of surveys and a face-to-face meeting, af- measurement of antiretinal antibodies, there is no ter which structured feedback was given for each round. Ex- universally standardized assay for antiretinal antibody perts were then encouraged to reconsider their opinion in testing. Consequently, inconsistent diagnoses among light of the cumulative responses of other experts. This institutions or physicians may result. One study compared allowed experts to remain anonymous while considering the results of antiretinal antibody detection and the responses and opinions of the group and clarifying their measurement between 2 laboratories and found an overall opinions for others. To develop consensus, a survey of uve- concordance rate of any antiretinal antibodies detected itis specialists in the American Uveitis Society (AUS), a to be 64% with a very poor interobserver agreement face-to-face meeting (AIR Workshop) held at the National (kappa ¼0.13). Further, the antiretinal antibody– Eye Institute, and 2 iterations of an expert panel survey specific concordance rate was a mere 36%.6 Currently, were used (Figure 1). This study was in adherence to the te- only 1 center in the United States provides antiretinal anti- nets of the Declaration of Helsinki. body testing commercially through a CLIA (clinical labo- ratory improvement amendments)-certified laboratory AMERICAN UVEITIS SOCIETY MEMBER SURVEY: (Ocular Immunology Laboratory, Casey Eye Institute, Consensus development began with a 10-question survey Oregon Health & Science University).7 To establish diag- of AUS members to gauge the understanding of autoim- nostic criteria, promote collaboration, and advance our un- mune retinopathies among uveitis specialists. The survey derstanding of AIR, the development of a standardized was developed electronically (Survey Monkey,
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