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1. Ocular Syphilis

Author

Butler, Nicholas J., Sobrin, Lucia, Section editor, Albert, Daniel M., editor, Miller, Joan W., editor, Azar, Dimitri T., editor, and Young, Lucy H., editor

Published
2022
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3. Dual-Energy X-Ray Absorptiometry Scan Utilization and Skeletal Fragility Among Non-Infectious Uveitis Patients Exposed to Oral Glucocorticoids.

Author

Butler, Nicholas J., Cohen, Devin, Yu, Yinxi, Kempen, John H., Sobrin, Lucia, and VanderBeek, Brian L.

Subjects
*DUAL-energy X-ray absorptiometry, *BONE health, *RHEUMATOID arthritis, *MEDICAL screening, *UVEITIS
Abstract

Currently, little is known regarding bone health surveillance for glucocorticoid-exposed non-infectious uveitis (NIU) patients or their baseline risks of skeletal fragility outcomes. Using claims data, we calculated rates of dual-energy x-ray absorptiometry (DXA) screening for glucocorticoid-exposed NIU and rheumatoid arthritis (RA) patients. Separately, we compared risks of skeletal fragility metrics amongst NIU patients, RA patients, and controls, independent of glucocorticoid use. The adjusted hazard ratio (aHR) of NIU patients to have a DXA scan was 0.64 (95% CI, 0.63–0.65; p <.001) compared to RA patients. The aHR for any skeletal fragility outcome amongst NIU patients was 0.97 (p <.02) compared to normal controls, while RA patients had excess risk (aHR, 1.15; p <.001). NIU patients are 36% less likely to receive a DXA scan after high-dose glucocorticoid exposure compared with RA patients. No elevated risk of osteoporosis for NIU patients was found compared to normal controls. [ABSTRACT FROM AUTHOR]

Published
2024
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4. Topical and Subcutaneous Interferon-Alpha for the Treatment of Refractory Inflammatory Macular Edema.

Author

Green, Michael B. and Butler, Nicholas J.

Subjects
*MACULAR edema, *INTERFERON alpha, *REFRACTORY materials, *LEUCOPENIA, *INTERFERONS, *THERAPEUTICS
Abstract

PurposeMethodsResultsConclusionsTo evaluate the efficacy of topical interferon alpha-2b (tIFN a2b) and subcutaneous pegylated interferon alpha-2a (peg-IFN a2a) in the treatment of refractory pseudophakic (PME) and uveitic (UME) macular edema.Retrospective case series of patients with PME or UME that was non-responsive to conventional therapies. Topical IFN a2b drops (1 MIU/ml) were commenced four times a day. Non-responders were offered treatment with subcutaneous peg-IFN a2a starting at 180 mcg weekly.Seven eyes of seven patients (three UME and four PME) were treated with tIFN a2b. Three eyes had complete ME resolution with tIFN treatment after a mean of 2.66 weeks (range 1–4 weeks) and no recurrence after a mean total course of 11.33 weeks (range 5–20 weeks). Two cases (both PME) had partial responses to tIFN treatment and two cases (both UME) failed to respond. Of the four eyes that incompletely responded to tIFN (treatment range 6 weeks to 4 months), three were treated with peg-IFN a2a, which invariably led to complete and sustained ME resolution. Adverse effects from topical treatment were mild and consisted mainly of superficial irritation. Adverse effects of subcutaneous treatment included nausea, vomiting, anorexia, and leukopenia, though none limited treatment.Topical IFNa-2b appears safe and effective in isolation or in conjunction with topical steroids for the treatment of inflammatory macular edema (IME) in about half of patients in our small series. All partial and non-responders had complete disease resolution with systemic IFN. Topical IFN a2b should be considered in patients with refractory IME. [ABSTRACT FROM AUTHOR]

Published
2024
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8. Consensus on the Diagnosis and Management of Nonparaneoplastic Autoimmune Retinopathy Using a Modified Delphi Approach

Author

Fox, Austin R, Gordon, Lynn K, Heckenlively, John R, Davis, Janet L, Goldstein, Debra A, Lowder, Careen Y, Nussenblatt, Robert B, Butler, Nicholas J, Dalal, Monica, Jayasundera, Thiran, Smith, Wendy M, Lee, Richard W, Adamus, Grazyna, Chan, Chi-Chao, Hooks, John J, Morgans, Catherine W, Detrick, Barbara, and Sen, H Nida

Subjects
Clinical Research, Eye Disease and Disorders of Vision, Autoantibodies, Autoantigens, Autoimmune Diseases, Consensus, Delphi Technique, Humans, Paraneoplastic Syndromes, Ocular, Retina, Retinal Diseases, Clinical Sciences, Opthalmology and Optometry, Public Health and Health Services, Ophthalmology & Optometry
Abstract

PurposeTo develop diagnostic criteria for nonparaneoplastic autoimmune retinopathy (AIR) through expert panel consensus and to examine treatment patterns among clinical experts.DesignModified Delphi process.MethodsA survey of uveitis specialists in the American Uveitis Society, a face-to-face meeting (AIR Workshop) held at the National Eye Institute, and 2 iterations of expert panel surveys were used in a modified Delphi process. The expert panel consisted of 17 experts, including uveitis specialists and researchers with expertise in antiretinal antibody detection. Supermajority consensus was used and defined as 75% of experts in agreement.ResultsThere was unanimous agreement among experts regarding the categorization of autoimmune retinopathies as nonparaneoplastic and paraneoplastic, including cancer-associated retinopathy and melanoma-associated retinopathy. Diagnostic criteria and tests essential to the diagnosis of nonparaneoplastic AIR and multiple supportive criteria reached consensus. For treatment, experts agreed that corticosteroids and conventional immunosuppressives should be used (prescribed) as first- or second-line treatments, though a consensus agreed that biologics and intravenous immunoglobulin were considered appropriate in the treatment of nonparaneoplastic AIR patients regardless of the stage of disease. Experts agreed that more evidence is needed to treat nonparaneoplastic AIR patients with long-term immunomodulatory therapy and that there is enough equipoise to justify randomized, placebo-controlled trials to determine if nonparaneoplastic AIR patients should be treated with long-term immunomodulatory therapy. Regarding antiretinal antibody detection, consensus agreed that a standardized assay system is needed to detect serum antiretinal antibodies. Consensus agreed that an ideal assay should have a 2-tier design and that Western blot and immunohistochemistry should be the methods used to identify antiretinal antibodies.ConclusionsConsensus was achieved using a modified Delphi process to develop diagnostic criteria for nonparaneoplastic AIR. There is enough equipoise to justify randomized, placebo-controlled trials to determine whether patients with nonparaneoplastic AIR should be treated with long-term immunomodulatory therapy. Efforts to develop a standardized 2-tier assay system for the detection of antiretinal antibodies have been initiated as a result of this study.

Published
2016

9. Dissociations of the Fluocinolone Acetonide Implant: The Multicenter Uveitis Steroid Treatment (MUST) Trial and Follow-up Study

Author

Holbrook, Janet T, Sugar, Elizabeth A, Burke, Alyce E, Vitale, Albert T, Thorne, Jennifer E, Davis, Janet L, Jabs, Douglas A, Jaffe, Glenn J, Branchaud, Brenda, Hahn, Paul, Koreen, Larry, Lad, Eleonora M, Lin, Phoebe, Martel, Joseph Nissim, Serrano, Neha, Skalak, Cindy, Vajzovic, Lejla, Baer, Claxton, Bryant, Joyce, Chavala, Sai, Cusick, Michael, Day, Shelley, Dayani, Pouya, Ehlers, Justis, Kesen, Muge, Lee, Annie, Melamud, Alex, Qureshi, Jawad A, Scott, Adrienne Williams, See, Robert F, Shuler, Robert K, Wood, Megan, Yeh, Steven, Fernandes, Alcides, Gibbs, Deborah, Leef, Donna, Martin, Daniel F, Srivastava, Sunil, Dunn, James P, Begum, Hosne, Boring, Jeff, Brotherson, Kristen L, Burkholder, Bryn, Butler, Nicholas J, Cain, Dennis, Cook, Mary A, Emmert, David, Graul, Janis R, Herring, Mark, Laing, Ashley, Leung, Theresa G, Mahon, Michael C, Moradi, Ahmafreza, Nwankwo, Antonia, Ostheimer, Trucian L, Reed, Terry, Arnold, Ellen, Barnabie, Patricia M, Belair, Marie-Lynn, Bolton, Stephen G, Brodine, Joseph B, Brown, Diane M, Brune, Lisa M, Galor, Anat, Gan, Theresa, Jacobowitz, Adam, Kapoor, Meera, Kedhar, Sanjay, Kim, Stephen, Leder, Henry A, Livingston, Alison G, Morton, Yavette, Nolan, Kisten, Peters, George B, Soto, Priscilla, Stevenson, Ricardo, Tarver-Carr, Michelle, Wang, Yue, Foster, C Stephen, Anesi, Stephen D, Bruner, Linda, Ceron, Olga, Hinkle, David M, Persons, Nancy, Wentworth, Bailey, Acevedo, Sarah, Anzaar, Fahd, Cesca, Tom, Contero, Angelica, Fitzpatrick, Kayleigh, Goronga, Faith, Johnson, Jyothir, Lebron, Karina Q, Marvell, Danielle, Morgan, Chandra, Patel, Nita, Pinto, Jennifer, Siddique, Sana S, Sprague, Janet, and Yilmaz, Taygan

Subjects
Clinical Trials and Supportive Activities, Brain Disorders, Eye Disease and Disorders of Vision, Bioengineering, Clinical Research, Prevention, Neurosciences, Eye, Adolescent, Adult, Aged, Aged, 80 and over, Drug Implants, Equipment Failure, Female, Fluocinolone Acetonide, Follow-Up Studies, Foreign-Body Migration, Glucocorticoids, Humans, Intravitreal Injections, Male, Middle Aged, Postoperative Complications, Reoperation, Risk Factors, Time Factors, Uveitis, Visual Acuity, Multicenter Uveitis Steroid Treatment (MUST) Trial Research Group, Clinical Sciences, Opthalmology and Optometry, Public Health and Health Services, Ophthalmology & Optometry
Abstract

PurposeTo describe fluocinolone acetonide implant dissociations in the Multicenter Uveitis Steroid Treatment (MUST) Trial.DesignRandomized clinical trial with extended follow-up.MethodsReview of data collected on the first implant in the eye(s) of participants. Dissociation was defined as the drug pellet no longer being affixed to the strut and categorized as spontaneous or surgically related.ResultsA total of 250 eyes (146 patients) had at least 1 implant placed. Median follow-up time after implant placement was 6 years (range 0.5-9.2 years). Thirty-four dissociations were reported in 30 participants. There were 22 spontaneous events in 22 participants; 6-year cumulative risk of a spontaneous dissociation was 4.8% (95% confidence interval [CI]: 2.4%-9.1%). The earliest event occurred 4.8 years after placement. Nine of 22 eyes with data had a decline in visual acuity ≥5 letters temporally related to the dissociation. Thirty-nine implant removal surgeries were performed, 33 with replacement. Twelve dissociations were noted during implant removal surgeries in 10 participants (26%, 95% CI 15%-48%); 5 of these eyes had a decline in visual acuity ≥5 letters after surgery. The time from implant placement to removal surgery was longer for the surgeries at which dissociated implants were identified than for those without one (5.7 vs 3.7 years, P < .001). Overall, visual acuity declined 15 or more letters from pre-implant values in 22% of affected eyes; declines were frequently associated with complications of uveitis or its treatment.ConclusionThere is an increasing risk of dissociation of Retisert implants during follow-up; the risk is greater with removal/exchange surgeries, but the risk of both spontaneous and surgically related events increases with longevity of the implants. In 22% of affected eyes visual acuity declined by 15 letters. In the context of eyes with moderate to severe uveitis for years, this rate is not unexpected.

Published
2016

10. Factors Predicting Visual Acuity Outcome in Intermediate, Posterior, and Panuveitis: The Multicenter Uveitis Steroid Treatment (MUST) Trial

Author

Kempen, John H, Van Natta, Mark L, Altaweel, Michael M, Dunn, James P, Jabs, Douglas A, Lightman, Susan L, Thorne, Jennifer E, Holbrook, Janet T, Jaffe, Glenn J, Branchaud, Brenda, Hahn, Paul, Koreen, Larry, Lad, Eleonora M, Lin, Phoebe, Martel, Joseph Nissim, Serrano, Neha, Skalak, Cindy, Vajzovic, Lejla, Baer, Claxton, Bryant, Joyce, Chavala, Sai, Cusick, Michael, Day, Shelley, Dayani, Pouya, Ehlers, Justis, Kesen, Muge, Lee, Annie, Melamud, Alex, Qureshi, Jawad A, Scott, Adrienne Williams, See, Robert F, Shuler, Robert K, Wood, Megan, Yeh, Steven, Fernandes, Alcides, Gibbs, Deborah, Leef, Donna, Martin, Daniel F, Srivastava, Sunil, Begum, Hosne, Boring, Jeff, Brotherson, Kristen L, Burkholder, Bryn, Butler, Nicholas J, Cain, Dennis, Cook, Mary A, Emmert, David, Graul, Janis R, Herring, Mark, Laing, Ashley, Leung, Theresa G, Mahon, Michael C, Moradi, Ahmafreza, Nwankwo, Antonia, Ostheimer, Trucian L, Reed, Terry, Arnold, Ellen, Barnabie, Patricia M, Belair, Marie-Lynn, Bolton, Stephen G, Brodine, Joseph B, Brown, Diane M, Brune, Lisa M, Galor, Anat, Gan, Theresa, Jacobowitz, Adam, Kapoor, Meera, Kedhar, Sanjay, Kim, Stephen, Leder, Henry A, Livingston, Alison G, Morton, Yavette, Nolan, Kisten, Peters, George B, Soto, Priscilla, Stevenson, Ricardo, Tarver-Carr, Michelle, Wang, Yue, Foster, C Stephen, Anesi, Stephen D, Bruner, Linda, Ceron, Olga, Hinkle, David M, Persons, Nancy, Wentworth, Bailey, Acevedo, Sarah, Anzaar, Fahd, Cesca, Tom, Contero, Angelica, Fitzpatrick, Kayleigh, Goronga, Faith, Johnson, Jyothir, Lebron, Karina Q, Marvell, Danielle, Morgan, Chandra, Patel, Nita, Pinto, Jennifer, Siddique, Sana S, and Sprague, Janet

Subjects
Clinical Trials and Supportive Activities, Clinical Research, Eye Disease and Disorders of Vision, 6.1 Pharmaceuticals, Evaluation of treatments and therapeutic interventions, Eye, Aged, Drug Implants, Female, Follow-Up Studies, Glucocorticoids, Humans, Male, Middle Aged, Panuveitis, Time Factors, Tomography, Optical Coherence, Treatment Outcome, Visual Acuity, Multicenter Uveitis Steroid Treatment (MUST) Trial Research Group, Clinical Sciences, Opthalmology and Optometry, Public Health and Health Services, Ophthalmology & Optometry
Abstract

PurposeTo identify factors associated with best-corrected visual acuity (BCVA) presentation and 2-year outcome in 479 intermediate, posterior, and panuveitic eyes.DesignCohort study using randomized controlled trial data.MethodsMulticenter Uveitis Steroid Treatment (MUST) Trial masked BCVA measurements at baseline and at 2 years follow-up used gold-standard methods. Twenty-three clinical centers documented characteristics per protocol, which were evaluated as potential predictive factors for baseline BCVA and 2-year change in BCVA.ResultsBaseline factors significantly associated with reduced BCVA included age ≥50 vs 10 vs grade 0; cataract; macular thickening; and exudative retinal detachment. Over 2 years, eyes better than 20/50 and 20/50 or worse at baseline improved, on average, by 1 letter (P = .52) and 10 letters (P < .001), respectively. Both treatment groups and all sites of uveitis improved similarly. Factors associated with improved BCVA included resolution of active AC cells, resolution of macular thickening, and cataract surgery in an initially cataractous eye. Factors associated with worsening BCVA included longer duration of uveitis (6-10 or >10 vs

Published
2015

15. Factors Predicting Visual Acuity Outcome in Intermediate, Posterior, and Panuveitis: The Multicenter Uveitis Steroid Treatment (MUST) Trial

Author

Jaffe, Glenn J., Branchaud, Brenda, Hahn, Paul, Koreen, Larry, Lad, Eleonora (Nora) M., Lin, Phoebe, Martel, Joseph Nissim, Serrano, Neha (Shah), Skalak, Cindy, Vajzovic, Lejla, Baer, Claxton, Bryant, Joyce, Chavala, Sai, Cusick, Michael, Day, Shelley, Dayani, Pouya, Ehlers, Justis, Kesen, Muge, Lee, Annie, Melamud, Alex, Qureshi, Jawad A., Scott, Adrienne Williams, See, Robert F., Shuler, Robert K., Wood, Megan, Yeh, Steven, Fernandes, Alcides, Gibbs, Deborah, Leef, Donna, Martin, Daniel F., Srivastava, Sunil, Dunn, James P., Begum, Hosne, Boring, Jeff, Brotherson, Kristen L., Burkholder, Bryn, Butler, Nicholas J., Cain, Dennis, Cook, Mary A., Emmert, David, Graul, Janis R., Herring, Mark, Laing, Ashley, Leung, Theresa G., Mahon, Michael C., Moradi, Ahmafreza, Nwankwo, Antonia, Ostheimer, Trucian L., Reed, Terry, Arnold, Ellen, Barnabie, Patricia M., Belair, Marie-Lynn, Bolton, Stephen G., Brodine, Joseph B., Brown, Diane M., Brune, Lisa M., Galor, Anat, Gan, Theresa, Jacobowitz, Adam, Kapoor, Meera, Kedhar, Sanjay, Kim, Stephen, Leder, Henry A., Livingston, Alison G., Morton, Yavette, Nolan, Kisten, Peters, George B., Soto, Priscilla, Stevenson, Ricardo, Tarver-Carr, Michelle, Wang, Yue, Foster, C. Stephen, Anesi, Stephen D., Bruner, Linda, Ceron, Olga, Hinkle, David M., Persons, Nancy, Wentworth, Bailey, Acevedo, Sarah, Anzaar, Fahd, Cesca, Tom, Contero, Angelica, Fitzpatrick, Kayleigh, Goronga, Faith, Johnson, Jyothir, Lebron, Karina Q., Marvell, Danielle, Morgan, Chandra, Patel, Nita, Pinto, Jennifer, Siddique, Sana S., Sprague, Janet, Yilmaz, Taygan, Sen, H. Nida, Bono, Michael, Cunningham, Denise, Hayes, Darryl, Koutsandreas, Dessie, Nussenblatt, Robert B., Sherry, Patti R., Short, Gregory L., Smith, Wendy, Temple, Alana, Bamji, Allison, Coleman, Hanna, Davuluri, Geetaniali, Faia, Lisa, Gottlieb, Chloe, Jirawuthiworavong, Guy V., Lew, Julie C., Mercer, Richard, Obiyor, Dominic, Perry, Cheryl H., Potapova, Natalia, Weichel, Eric, Wroblewski, Keith J., Latkany, Paul A., Coonan, Corinne, Honda, Andrea, Lorenzo-Latkany, Monica, Masini, Robert, Morell, Susan, Nguyen, Angela, Badamo, Jason, Boyd, Kenneth M., Enos, Matthew, Gallardo, Jenny, Jarczynski, Jacek, Lee, Ji Yun, McGrosky, Mirjana, Nour, Ann, Sanchez, Meredith, Steinberg, Kate, Stawell, Richard J., Breayley, Lisa, D'Sylva, Carly, Glatz, Elizabeth, Hodgson, Lauren, Lim, Lyndell, Ling, Cecilia, McIntosh, Rachel, Morrison (Ewing), Julie, Newton, Andrew, Sanmugasundram, Sutha, Smallwood, Richard, Zamir, Ehud, Hunt, Nicola, Jones, Lisa, Koukouras, Ignatios, Williams, Suzanne, Merrill, Pauline T., Carns, Danielle, Richine, Len, Voskuil-Marre, Denise L., Woo, Kisung, Gaynes, Bruce, Giannoulis, Christina, Hulvey, Pam, Kernbauer, Elaine, Khan, Heena S., Levine, Sarah J., Toennessen, Scott, Tonner, Eileen, Wang, Robert C., Aguado, Hank, Arceneaux, Sally, Duignan, Karen, Fish, Gary E., Hesse, Nick, Jaramillo, Diana, Mackens, Michael, Arnwine, Jean, Callanan, David, Cummings, Kimberly, Gray, Keith, Howden, Susie, Mutz, Karin, Sanchez, Brenda, Lightman, Susan, Ismetova, Filis, Prytherch, Ashley, Seguin-Greenstein, Sophie, Tomkins, Oren, Bar, Asat, Edwards, Kate, Joshi, Lavanish, Moraji, Jiten, Samy, Ahmed, Stubbs, Timothy, Taylor, Simon, Towler, Hamish, Tronnberg, Rebecca, Holland, Gary N., Almanzor, Robert D., Castellanos, Jose, Hubschman, Jean Pierre, Johiro, Ann K., Kukuyev, Alla, Levinson, Ralph D., McCannel, Colin A., Ransome, Susan S., Gonzales, Christine R., Gupta, Anurag, Kalyani, Partho S., Kapamajian, Michael A., Kappel, Peter J., Arcinue, Cheryl, Chuang, Janne, Barteselli, Giulio, Currie, Glenn, Mendoza, Veronica, Powell, Debbie, Clark, Tom, Cochran, Denine E., Freeman, William R., Hedaya, Joshua, Kemper, Tiara, Kozak, Igor, LeMoine, Jacqueline M., Loughran, Megan E., Magana, Luzandra, Mojana, Francesca, Morrison, Victoria, Nguyen, Vivian, Oster, Stephen F., Acharya, Nisha, Clay, David, Lee, Salena, Lew, Mary, Margolis, Todd P., Stewart, Jay, Wong, Ira G., Brown, Debra, Khouri, Claire M., Goldstein, Debra A., Birnbaum, Andrea, Degillio, Andrea, Rosa, Gemma De la, Ramirez, Carmen, Simjanowski, Evica, Skelly, Mariner, Castro-Malek, Anna L., Crooke, Catherine E., Huntley, Melody, Nash, Katrina, Niec, Marcia, Pyatetsky, Dimitry, Ramirez, Misel, Rozenbajgier, Zuzanna, Tessler, Howard H., Davis, Janet L., Albini, Thomas A., Chin, Marie, Castaño, Daniela, Elizondo, Ariana, Ho, Macy, Kovach, Jaclyn L., Lin, Richard C-S., Mandelcorn, Efrem, Nguyen, Jackie K-D., Pacini, Aura, Pineda, Susan, Pinto, David A., Rebimbas, Jose, Stepien, Kimberly E., Teran, Claudia, Elner, Susan G., Bernard, Hillary, Fournier, Linda, Godsey, Lindsay, Goings, Linda, Hackel, Richard, Hesselgrave, Moella, Jayasundera, K. Thiran, Prusak, Robert, Titus, Pamela, Bergeron, Melissa, Blosser, Reneé, Brown, Rebecca, Chrisman-McClure, Carrie, Gothrup, Julie R., Saxe, Stephen J., Sizemore, Deanna, Kempen, John H., Berger, James, Drossner, Sheri, DuPont, Joan C., Maguire, Albert M., Petner, Janice, Engelhard, Stephanie, Hopkins, Tim, Lo, Jonathan, McCall, Dawn, McRay, Monique, Salvo, Rebecca, Will, Daniel, Xu, Wei, Windsor, Elizabeth, Weeney, Laurel, Pavan, Peter R., Albritton, Ken, Leto, JoAnn, Madow, Brian, Mayor, Lori, Pautler, Scott E., Saxon, Wyatt, Soto, Judy, Goldstein, Burton, Klukoff, Amy, Lambright, Lucy, McDonald, Kim, Ortiz, Maria, Scymanky, Susan, Szalay, Dee Dee, Rao, Narsing, Davis, Tamara, Douglass, Jackie, Linton, Judith, Padilla, Margaret, Ramos, Sylvia, Rao, Narsing A., Aguirre, Alexia, Chong, Lawrence, Cisneros, Lupe, Corona, Elizabeth, Eliott, Dean, Fawzi, Amani, Garcia, Jesse, Khurana, Rahul, Lim, Jennifer, Mead, Rachel, Tsai, Julie H., Vitale, Albert, Bernstein, Paul S., Carlstrom, Bonnie, Gilman, James, Hanseen, Sandra, Morris, Paula, Ramirez, Diana, Wegner, Kimberley, Sheppard, John D., Anthony, Brianne, Casper, Amber, Felix-Kent, Lisa, Fernandez, Jeanette, Johnson, Tari, Scoper, Stephen V., Cole, R. Denise, Crawford, Nancy, Franklin, Lisa, Hamelin, Krista, Martin, Jen, Marx, Rebecca, Schultz, Gregory, Webb, Joseph, Yeager, Pamela, Kim, Rosa Y., Benz, Matthew S., Brown, David M., Chen, Eric, Fish, Richard H., Kegley, Eric, Shawver, Laura, Wong, Tien P., De La Garza, Rebecca, Friday (Hay), Shayla, Rao, P. Kumar, Adcock, Eve, Apte, Rajendra S., Baladenski, Amy, Curtis, Rhonda, Gould, Sarah, Hebden, Amanda, Kambarian, Jamie, Meyer, Charla, Pistorius, Sam, Quinn, Melanie, Rathert, Greg, Blinder, Kevin J., Hartz, Ashley, Light, Pam, Shah, Gaurav K., VanGelder, Russell, Jabs, Douglas A., Altaweel, Michael M., Holbrook, Janet T., Kurinij, Natalie, Brown, Diane, Prusakowski, Nancy, Thorne, Jennifer E., Hubbard, Larry, Wittes, Janet, Barlow, William E., Hochberg, Marc, Lyon, Alice T., Palestine, Alan G., Simon, Lee S., Rosenbaum, James T., Smith, Harmon, Davis, Janet, Thorne, Jennifer, Acharya, Nisha R., Vitale, Albert T., Boring, Jeffrey A., Alexander, Judith, Ng, Wai Ping, Friedman, David S., Adler, Anna, Burke, Alyce, Katz, Joanne, Reed, Susan, Ansari, Husam, Cohen, Nicholas, Modak, Sanjukta, Sugar, Elizabeth A., Burke, Alyce E., Drye, Lea T., Van Natta, Mark L., Frick, Kevin, Katz, JoAnn, Louis, Thomas A., Shade, David, Pascual, Karen, Slutsky-Sanon, Jill S., Allen, Amanda, Glomp, Colby, Hilal, Yasmin, Nieves, Melissa A., Stevens, Maria, Abreu, Francis, Casper, Anne Shanklin, Ewing, Cathleen, Hart, Adante, Lears, Andrea, Li, Shirley, Meinert, Jill, Morrison, Vinnette, Nowakowski, Deborah, Reyes, Girlie, Shade, Dave M., Smith, Jacqueline, Steuernagle, Karen, Van Natta, Mark, Venugopal, Vidya, Yu, Tsung, Chen, Paul, Collins, Karen, Dodge, John, Frick, Kevin D., Jackson, Rosetta, Jimenez, Christian, Landers, Ariel, Livingston, Hope, Meinert, Curtis L., Rayapudi, Sobharani, Shen, Weijiang, Shiflett, Charles, Smith, Rochelle, Tieman, Ada, Tonascia, James A., Zheng, Richard, Allan, James, Benz, Wendy K., Domalpally, Amitha, Johnson, Kristine A., Myers, Dawn J., Won Pak, Jeong, Reimers, James L., Chambers, Geoffrey, Christianson, Debra J., Fleischli, Margaret A., Freund, Jacquelyn, Gama, Vonnie, Gangaputra, Sapna, Glander, Kathleen E., Goulding, Anne, Hafford, Dennis, Harris, Susan E., Hubbard, Larry D., Joyce, Jeffrey M., Kruse, Christina N., Nagle, Lauren, Padden-Lechten, Gwyn E., Pohlman, Alyson, Remm, Amy, Shaw, Ruth A., Sivesind, Peggy, Thayer, Dennis, Treichel, Erika, Warren, Kelly J., Watson, Sheila M., Webster, Mary K., White, James K., Wilhelmson, Tara, Zhang, Grace, and Lightman, Susan L.

Published
2015
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19. The standardisation of uveitis nomenclature (SUN) project.

Author

Jabs, Douglas A., McCluskey, Peter, Palestine, Alan G., Thorne, Jennifer E., The Standardization of Uveitis Nomenclature Working Group, Accorinti, Massimo, Acharya, Nisha, Amer, Radgonde, Atmaca, Leyla S., Bar, Asaf, Barisani‐Asenbauer, Talin, Becker, Matthias D., Bélair, Marie‐Lyne, Belfort, Rubens, Bhatt, Nirali P., Biswas, Jyotirmay, Blodi, Barbara, Bodaghi, Bahram, Brézin, Antoine P., and Butler, Nicholas J.

Subjects
UVEITIS, EYE inflammation, MACHINE learning, TRANSLATIONAL research, IRIDOCYCLITIS
Abstract

The uveitides are a collection of over 30 diseases characterised by intraocular inflammation. Previous work demonstrated that the agreement among uveitis experts on diagnosis was modest at best with some pairs of experts having chance alone agreement on selected diseases. The Standardisation of Uveitis Nomenclature (SUN) is a17‐year collaboration among experts in uveitis, ocular image grading, informatics, and machine learning to improve clinical and translational uveitis research. The SUN "Developing Classification Criteria for the Uveitides" project used a rigorous, multi‐phase approach to develop classification criteria for 25 of the most common uveitic diseases. The project's phases were: (1) informatics; (2) case collection; (3) case selection; (4) machine learning; and (5) consensus review and publication. The results were classification criteria with a high degree of accuracy (93.3%–99.3% depending on anatomic class of the uveitis), the goal of which is to form the basis for future uveitis research. [ABSTRACT FROM AUTHOR]

Published
2022
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28. Cross-reactive microbial peptides can modulate HIV-specific CD8+ T cell responses

Author

Pohlmeyer, Christopher W., primary, Laskey, Sarah B., additional, Beck, Sarah E., additional, Xu, Daniel C., additional, Capoferri, Adam A., additional, Garliss, Caroline C., additional, May, Megan E., additional, Livingston, Alison, additional, Lichmira, Walt, additional, Moore, Richard D., additional, Leffell, M. Sue, additional, Butler, Nicholas J., additional, Thorne, Jennifer E., additional, Flynn, John A., additional, Siliciano, Robert F., additional, and Blankson, Joel N., additional

Published
2018
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31. Reply

Author

Fox, Austin R., primary, Gordon, Lynn K., additional, Heckenlively, John R., additional, Davis, Janet L., additional, Goldstein, Debra A., additional, Lowder, Careen Y., additional, Nussenblatt, Robert B., additional, Butler, Nicholas J., additional, Dalal, Monica, additional, Jayasundera, Thiran, additional, Smith, Wendy M., additional, Lee, Richard W., additional, Adamus, Grazyna, additional, Chan, Chi-Chao, additional, Hooks, John J., additional, Morgans, Catherine W., additional, Detrick, Barbara, additional, and Sen, H. Nida, additional

Published
2016
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32. RITUXIMAB THERAPY FOR REFRACTORY ORBITAL INFLAMMATION: RESULTS OF A PHASE I/II DOSE-RANGING RANDOMIZED CLINICAL TRIAL

Author

Suhler, Eric B., Lim, Lyndell L., Beardsley, Robert M., Giles, Tracy R., Pasadhika, Sirichai, Lee, Shelly T., Sardos, Alexandre de Saint, Butler, Nicholas J., Smith, Justine R., and Rosenbaum, James T.

Subjects
Adult, Aged, 80 and over, Male, Time Factors, Dose-Response Relationship, Drug, Visual Acuity, Middle Aged, Antigens, CD20, Severity of Illness Index, Article, Antibodies, Monoclonal, Murine-Derived, Treatment Outcome, Double-Blind Method, Recurrence, Orbital Pseudotumor, Humans, Immunologic Factors, Female, Infusions, Intravenous, Rituximab, Aged, Follow-Up Studies, Retrospective Studies
Abstract

Orbital inflammation is a potentially blinding and disfiguring disease process that is often treated with systemic corticosteroids and immunosuppression; better treatments are needed.To determine whether rituximab, a monoclonal antibody against the B-lymphocyte antigen CD20, is effective in the treatment of refractory orbital inflammation.A dose-ranging, randomized, double-masked phase 1/2 clinical trial was conducted at a tertiary referral ophthalmology clinic. Ten individuals with orbital inflammation refractory to systemic corticosteroids and at least 1 other immunosuppressive agent were enrolled from January 2007 to March 2010.Rituximab infusions were administered on study days 1 and 15 at doses of either 500 mg or 1000 mg. Initial responders with recurrent inflammation after week 24 were permitted reinfusion with an additional cycle of 2 open-label 1000-mg rituximab infusions.The primary outcomes were reduction of inflammation measured with a validated orbital disease grading scale and corticosteroid dose reduction by at least 50%. The secondary outcomes were visual acuity, reduction in pain, and participant- and physician-reported global health assessment.Of 10 enrolled patients, 7 demonstrated improvement on the orbital disease grading scale at the 24-week end point with rituximab therapy. Of these 7 individuals, 4 were receiving corticosteroids at study inception and all achieved successful dose reduction. For the secondary outcome measures in the 10 participants, 7 patients and 8 patients improved in self-rated and physician global health scores, respectively, and 7 patients had reduction in pain by 25% or more at 24 weeks. Four patients who were positive responders at the week 24 end point experienced breakthrough inflammation after week 24 and received reinfusions between 24 and 48 weeks. Vision remained stable in all participants. Three of 10 patients had short-term objective or subjective worsening 2 to 8 weeks after receiving rituximab infusions, which was averted in subsequent patients with oral corticosteroids administered during the infusion and did not affect the eventual positive treatment outcome. No significant differences with regard to efficacy, toxicity, or likelihood of retreatment were noted between the dosing arms.Rituximab was safe and effective in 7 of 10 patients with noninfectious orbital disease, although 4 required reinfusion with rituximab to maintain control of orbital inflammation. Substantial toxicity was not noted. Rituximab should be considered in the treatment of refractory orbital inflammation.clinicaltrials.gov Identifier: NCT00415506.

Published
2014

33. Consensus on the Diagnosis and Management of Nonparaneoplastic Autoimmune Retinopathy Using a Modified Delphi Approach

Author

Fox, Austin R., primary, Gordon, Lynn K., additional, Heckenlively, John R., additional, Davis, Janet L., additional, Goldstein, Debra A., additional, Lowder, Careen Y., additional, Nussenblatt, Robert B., additional, Butler, Nicholas J., additional, Dalal, Monica, additional, Jayasundera, Thiran, additional, Smith, Wendy M., additional, Lee, Richard W., additional, Adamus, Grazyna, additional, Chan, Chi-Chao, additional, Hooks, John J., additional, Morgans, Catherine W., additional, Detrick, Barbara, additional, and Sen, H. Nida, additional

Published
2016
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35. Cross-reactive microbial peptides can modulate HIV-specific CD8+ T cell responses.

Author

Pohlmeyer, Christopher W., Laskey, Sarah B., Beck, Sarah E., Xu, Daniel C., Capoferri, Adam A., Garliss, Caroline C., May, Megan E., Livingston, Alison, Lichmira, Walt, Moore, Richard D., Leffell, M. Sue, Butler, Nicholas J., Thorne, Jennifer E., Flynn, John A., Siliciano, Robert F., and Blankson, Joel N.

Subjects
MICROBIAL peptides, HIV infection genetics, EPITOPES, MICROBIAL communities, MICROBIOLOGICAL chemistry
Abstract

Heterologous immunity is an important aspect of the adaptive immune response. We hypothesized that this process could modulate the HIV-1-specific CD8+ T cell response, which has been shown to play an important role in HIV-1 immunity and control. We found that stimulation of peripheral blood mononuclear cells (PBMCs) from HIV-1-positive subjects with microbial peptides that were cross-reactive with immunodominant HIV-1 epitopes resulted in dramatic expansion of HIV-1-specific CD8+ T cells. Interestingly, the TCR repertoire of HIV-1-specific CD8+ T cells generated by ex vivo stimulation of PBMCs using HIV-1 peptide was different from that of cells stimulated with cross-reactive microbial peptides in some HIV-1-positive subjects. Despite these differences, CD8+ T cells stimulated with either HIV-1 or cross-reactive peptides effectively suppressed HIV-1 replication in autologous CD4+ T cells. These data suggest that exposure to cross-reactive microbial antigens can modulate HIV-1-specific immunity. [ABSTRACT FROM AUTHOR]

Published
2018
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36. Rituximab Therapy for Refractory Scleritis

Author

Suhler, Eric B., primary, Lim, Lyndell L., additional, Beardsley, Robert M., additional, Giles, Tracy R., additional, Pasadhika, Sirichai, additional, Lee, Shelly T., additional, de Saint Sardos, Alexandre, additional, Butler, Nicholas J., additional, Smith, Justine R., additional, and Rosenbaum, James T., additional

Published
2014
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37. Tattoo-Associated Uveitis

Author

Ostheimer, Trucian A., primary, Burkholder, Bryn M., additional, Leung, Theresa G., additional, Butler, Nicholas J., additional, Dunn, James P., additional, and Thorne, Jennifer E., additional

Published
2014
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46. Update on Diagnosis and Treatment of CMV Retinitis.

Author

BUTLER, NICHOLAS J. and THORNE, JENNIFER E.

Subjects
CYTOMEGALOVIRUS retinitis treatment, CYTOMEGALOVIRUS disease diagnosis, OPHTHALMOSCOPY, EYE examination, GANCICLOVIR, THERAPEUTICS
Abstract

The article reviews current literature on cytomegalovirus (CMV) retinitis with attention directed to recent advances in the diagnosis and treatment of the disease, as of January 1, 2014. Topics discussed include diagnosis of CMV retinitis by ophthalmoscopic findings, ocular imaging and biochemical testing. Also discussed is management of the disease in HIV-AIDS and non-HIV patients including intravitreal, intravenous and oral anti virals including ganciclovir, cidofovir and foscarnet.

Published
2014

47. Stress hyperglycemia exacerbates inflammatory brain injury after stroke.

Author

Won SJ, Zhang Y, Butler NJ, Kim K, Mocanu E, Nzoutchoum OT, Lakkaraju R, Davis J, Ghosh S, and Swanson RA

Abstract

Post-stroke hyperglycemia occurs in 30% - 60% of ischemic stroke patients as part of the systemic stress response, but neither clinical evidence nor pre-clinical studies indicate whether post-stroke hyperglycemia affects stroke outcome. Here we investigated this issue using a mouse model of permanent ischemia. Mice were maintained either normoglycemic or hyperglycemic during the interval of 17 - 48 hours after ischemia onset. Post-stroke hyperglycemia was found to increase infarct volume, blood-brain barrier disruption, and hemorrhage formation, and to impair motor recovery. Post-stroke hyperglycemia also increased superoxide formation by peri-infarct microglia/macrophages. In contrast, post-stroke hyperglycemia did not increase superoxide formation or exacerbate motor impairment in p47 phox-/- mice, which cannot form an active superoxide-producing NADPH oxidase-2 complex. These results suggest that hyperglycemia occurring hours-to-days after ischemia can increase oxidative stress in peri-infarct tissues by fueling NADPH oxidase activity in reactive microglia/macrophages, and by this mechanism contribute to worsened functional outcome.

Published
2024
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48. α-synuclein aggregates induce c-Abl activation and dopaminergic neuronal loss by a feed-forward redox stress mechanism.

Author

Ghosh S, Won SJ, Wang J, Fong R, Butler NJM, Moss A, Wong C, Pan J, Sanchez J, Huynh A, Wu L, Manfredsson FP, and Swanson RA

Subjects
Animals, Cysteine, Dopamine, Dopaminergic Neurons metabolism, Mice, Oxidation-Reduction, Substantia Nigra metabolism, Parkinson Disease drug therapy, alpha-Synuclein metabolism
Abstract

Oxidative stress and α-synuclein aggregation both drive neurodegeneration in Parkinson's disease, and the protein kinase c-Abl provides a potential amplifying link between these pathogenic factors. Suppressing interactions between these factors may thus be a viable therapeutic approach for this disorder. To evaluate this possibility, pre-formed α-synuclein fibrils (PFFs) were used to induce α-synuclein aggregation in neuronal cultures. Exposure to PFFs induced oxidative stress and c-Abl activation in wild-type neurons. By contrast, α-synuclein - deficient neurons, which cannot form α-synuclein aggregates, failed to exhibit either oxidative stress or c-Abl activation. N-acetyl cysteine, a thiol repletion agent that supports neuronal glutathione metabolism, suppressed the PFF - induced redox stress and c-Abl activation in the wild-type neurons, and likewise suppressed α-synuclein aggregation. Parallel findings were observed in mouse brain: PFF-induced α-synuclein aggregation in the substantia nigra was associated with redox stress, c-Abl activation, and dopaminergic neuronal loss, along with microglial activation and motor impairment, all of which were attenuated with oral N-acetyl cysteine. Similar results were obtained using AAV-mediated α-synuclein overexpression as an alternative means of driving α-synuclein aggregation in vivo. These findings show that α-synuclein aggregates induce c-Abl activation by a redox stress mechanism. c-Abl activation in turn promotes α-synuclein aggregation, in a feed-forward interaction. The capacity of N-acetyl cysteine to interrupt this interaction adds mechanistic support its consideration as a therapeutic in Parkinson's disease., (Published by Elsevier Ltd.)

Published
2021
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