Visual Field Outcomes for the Idiopathic Intracranial Hypertension Treatment Trial (IIHTT)

Michael Wall, Chris A Johnson, Kimberly E Cello, K D Zamba, Michael P McDermott, John L Keltner, NORDIC Idiopathic Intracranial Hypertension Study Group, Rudrani Banik, Sanjay Kedhar, Flora Levin, Jonathan Feistmann, Katy Tai, Alex Yang, Karen Tobias, Melissa Rivas, Lorena Dominguez, Violete Perez, Reid Longmuir, Matthew Thurtell, Trina Eden, Randy Kardon, Robert Lesser, Yanina O'Neil, Sue Heaton, Nathalie Gintowt, Danielle Rudich, Kathleen Digre, Judith Warner, Barbara Hart, Kimberley Wegner, Bonnie Carlstrom, Susan Allman, Bradley Katz, Anne Haroldsen, Byron L Lam, Joshua Pasol, Potyra R Rosa, Alexis Morante, Jennifer Verriotto, David Katz, Tracy Asbury, Robert Gerwin, Mary Barnett, Steven Hamilton, Caryl Tongco, Beena Gangadharan, Eugene May, Anil Patel, Bradley Farris, R Michael Siatkowsk, Heather Miller, Vanessa Bergman, Kammerin White, Steven O'Dell, Joseph Andrezik, Timothy Tytle, Kenneth Shindler, Joan Dupont, Rebecca Salvo, Sheri Drossner, Susan Ward, Jonathan Lo, Stephanie Engelhard, Elizabeth Windsor, Sami Khella, Madhura Tamhankar, Gregory Van Stavern, Jamie Kambarian, Renee Van Stavern, Karen Civitelli, J Banks Shepherd, Beau B Bruce, Nancy J Newman, Judy Brower, Linda Curtis, Michael Vaphiades, Karen Searcey, Lanning Kline, Roy McDonald, Syndee J Givre, Tippi Hales, Keisha Fuller, Kenneth M Carnes, Kimberly James, Marisol Ragland, Sophia M Chung, Dawn M Govreau, John T Lind, Zoe Williams, George O'Gara, Kari Steinmetz, Karen Skrine, Elisabeth Carter, Rajeev Ramchandran, Steven Katz, Marc Criden, Gina Coman, John McGregor, Andrea Inman, Prem S Subramanian, Paul N Hoffman, Marianne Medura, M Michaele Hartnett, Madiha Siddiqui, Diane Brown, Ellen Arnold, Jeff Boring, Neil R Miller, Peter Quiros, Sylvia Ramos, Margaret Padilla, Lupe Cisneros, Anne Kao, Carlos Filipe Chicani, Kevin Na, Rosa Tang, Laura Frishman, Priscilla Cajavilca, Sheree Newland, Liat Gantz, Maria Guillermo Prieto, Anastas Pass, Nicky R Holdeman, Michael S Lee, Helen Roemhild, Wendy Elasky, Anne Holleschau, Jody Fissgus, Jamie Walski, Andrew Harrison, Julie Falardeau, William Hills, Cristi Bryant, Donna Kim, Rebecca Armour, Lori Higginbotham, Steven A Newman, Kristina Holbrook, Laura D Cook, Holly Bacon, Janis Beall, Thomas Goddard, William Hall, Debbie Hamilton, Alan Lyon, William Fletcher, Suresh Subramaniam, Jeannie Reimer, Jeri Nickerson, Fiona Costello, Vivian Rismondo-Stankovich, Maureen Flanagan, Allison Jensen, Patrick Sibony, Ann Marie Lavorna, Mary Mladek, Ruth Tenzler, Robert Honkanen, Jill Miller-Horn, Lauren Krupp, Joseph Rizzo, Dean Cestari, Neal Snebold, Brian Vatcher, Christine Matera, Edward Miretsky, Judith Oakley, Josyane Dumser, Tim Alperen, Sandra Baptista-Pires, Ursula Bator, Barbara Barrett, Charlene Callahan, Sarah Brett, Kamella Zimmerman, Marcia Grillo, Karen Capaccioli, M Tariq Bhatti, LaToya Greene, Maria Cecilia Santiago-Turla, Noreen McClain, Mays El-Dairi, Martha Schatz, John E Carter, Daniel Mojica, Joan Smith, Yolanda Trigo, Sherry Slayman Kellogg, Alexandra Martinez, Paul Comeau, Andres Sanchez, Nathan McCarthy, Erika Perez, Carlos Bazan, Charles Maitland, H Logan Brooks Jr, Ronda Gorsica, Brian Sherman, Joel Kramer, Larry Frohman, Amanda Ribeiro, Kathryn Boschert, Yu fei Tu, Susan Rivera, Roger Turbin, Martin ten Hove, Adriana Breen, Craig Simms, Mary Kemp, Jim Farmer, Robert Granadier, Tammy Osentoski, Kristi Cumming, Bobbie Lewis, Lori Stec, Jorge C Kattah, John Pula, Mary Rose Buttice, Kimberly DuPage, Kimberly Cooley, Judith Beck, Lynn Bannon, Cynthia Guede, Luis Mejico, Melissa Ko, Burk Jubelt, Megan Grosso, Mark Chilton, Mary Lou Watson, Jennifer Moore, Tim Martin, Cara Everhart, Joan Fish, Lori Cooke, J Paul Dickinson, Marie D Acierno, Rachelle Watts, Amy Thomassie, Aravinda Rao, Trisha Mary Chiasson, Janet C Rucker, Christine Hannigan, Ilana Katz-Sand, De-epali Rajguru, Sachin Kedar, Nubia Vega, Stephanie Morris, Andrew Pearson, Mike Hanson, Betty Kovacs, Richard Weil, Xavier Pi-Sunyer, Steven Feldon, William Fisher, Dorothea Castillo, Valerie Davis, Lourdes Fagan, Rachel Hollar, Tammy Keenan, Peter MacDowell, John Keltner, Kim Plumb, Laura Leming, John S Werner, Danielle Harvey, Chris Johnson, John Keltner, John S Werner, Kim Plumb, Laura Leming, Jan Bausch, Shan Gao, Xin Tu, Hua He, Arthur Watts, Debbie Baker, Radu Constantinescu, Karen Helles, Nichole McMullen, Bev Olsen, Larry Preston, Victoria Snively, Ann Stoutenburg, Deborah Friedman, O Iyore Ayanru, Elizabeth-Ann Moss, Pravin Patel, Richard Mills, Maureen Maguire, William Hart Jr, Joanne Katz, David Kaufman, Cynthia McCarthy, John Selhorst, Kathleen Digre, James Corbett, Neil R Miller, Richard Mills, Michael Wall, Chris A Johnson, Kimberly E Cello, K D Zamba, Michael P McDermott, John L Keltner, NORDIC Idiopathic Intracranial Hypertension Study Group, Rudrani Banik, Sanjay Kedhar, Flora Levin, Jonathan Feistmann, Katy Tai, Alex Yang, Karen Tobias, Melissa Rivas, Lorena Dominguez, Violete Perez, Reid Longmuir, Matthew Thurtell, Trina Eden, Randy Kardon, Robert Lesser, Yanina O'Neil, Sue Heaton, Nathalie Gintowt, Danielle Rudich, Kathleen Digre, Judith Warner, Barbara Hart, Kimberley Wegner, Bonnie Carlstrom, Susan Allman, Bradley Katz, Anne Haroldsen, Byron L Lam, Joshua Pasol, Potyra R Rosa, Alexis Morante, Jennifer Verriotto, David Katz, Tracy Asbury, Robert Gerwin, Mary Barnett, Steven Hamilton, Caryl Tongco, Beena Gangadharan, Eugene May, Anil Patel, Bradley Farris, R Michael Siatkowsk, Heather Miller, Vanessa Bergman, Kammerin White, Steven O'Dell, Joseph Andrezik, Timothy Tytle, Kenneth Shindler, Joan Dupont, Rebecca Salvo, Sheri Drossner, Susan Ward, Jonathan Lo, Stephanie Engelhard, Elizabeth Windsor, Sami Khella, Madhura Tamhankar, Gregory Van Stavern, Jamie Kambarian, Renee Van Stavern, Karen Civitelli, J Banks Shepherd, Beau B Bruce, Nancy J Newman, Judy Brower, Linda Curtis, Michael Vaphiades, Karen Searcey, Lanning Kline, Roy McDonald, Syndee J Givre, Tippi Hales, Keisha Fuller, Kenneth M Carnes, Kimberly James, Marisol Ragland, Sophia M Chung, Dawn M Govreau, John T Lind, Zoe Williams, George O'Gara, Kari Steinmetz, Karen Skrine, Elisabeth Carter, Rajeev Ramchandran, Steven Katz, Marc Criden, Gina Coman, John McGregor, Andrea Inman, Prem S Subramanian, Paul N Hoffman, Marianne Medura, M Michaele Hartnett, Madiha Siddiqui, Diane Brown, Ellen Arnold, Jeff Boring, Neil R Miller, Peter Quiros, Sylvia Ramos, Margaret Padilla, Lupe Cisneros, Anne Kao, Carlos Filipe Chicani, Kevin Na, Rosa Tang, Laura Frishman, Priscilla Cajavilca, Sheree Newland, Liat Gantz, Maria Guillermo Prieto, Anastas Pass, Nicky R Holdeman, Michael S Lee, Helen Roemhild, Wendy Elasky, Anne Holleschau, Jody Fissgus, Jamie Walski, Andrew Harrison, Julie Falardeau, William Hills, Cristi Bryant, Donna Kim, Rebecca Armour, Lori Higginbotham, Steven A Newman, Kristina Holbrook, Laura D Cook, Holly Bacon, Janis Beall, Thomas Goddard, William Hall, Debbie Hamilton, Alan Lyon, William Fletcher, Suresh Subramaniam, Jeannie Reimer, Jeri Nickerson, Fiona Costello, Vivian Rismondo-Stankovich, Maureen Flanagan, Allison Jensen, Patrick Sibony, Ann Marie Lavorna, Mary Mladek, Ruth Tenzler, Robert Honkanen, Jill Miller-Horn, Lauren Krupp, Joseph Rizzo, Dean Cestari, Neal Snebold, Brian Vatcher, Christine Matera, Edward Miretsky, Judith Oakley, Josyane Dumser, Tim Alperen, Sandra Baptista-Pires, Ursula Bator, Barbara Barrett, Charlene Callahan, Sarah Brett, Kamella Zimmerman, Marcia Grillo, Karen Capaccioli, M Tariq Bhatti, LaToya Greene, Maria Cecilia Santiago-Turla, Noreen McClain, Mays El-Dairi, Martha Schatz, John E Carter, Daniel Mojica, Joan Smith, Yolanda Trigo, Sherry Slayman Kellogg, Alexandra Martinez, Paul Comeau, Andres Sanchez, Nathan McCarthy, Erika Perez, Carlos Bazan, Charles Maitland, H Logan Brooks Jr, Ronda Gorsica, Brian Sherman, Joel Kramer, Larry Frohman, Amanda Ribeiro, Kathryn Boschert, Yu fei Tu, Susan Rivera, Roger Turbin, Martin ten Hove, Adriana Breen, Craig Simms, Mary Kemp, Jim Farmer, Robert Granadier, Tammy Osentoski, Kristi Cumming, Bobbie Lewis, Lori Stec, Jorge C Kattah, John Pula, Mary Rose Buttice, Kimberly DuPage, Kimberly Cooley, Judith Beck, Lynn Bannon, Cynthia Guede, Luis Mejico, Melissa Ko, Burk Jubelt, Megan Grosso, Mark Chilton, Mary Lou Watson, Jennifer Moore, Tim Martin, Cara Everhart, Joan Fish, Lori Cooke, J Paul Dickinson, Marie D Acierno, Rachelle Watts, Amy Thomassie, Aravinda Rao, Trisha Mary Chiasson, Janet C Rucker, Christine Hannigan, Ilana Katz-Sand, De-epali Rajguru, Sachin Kedar, Nubia Vega, Stephanie Morris, Andrew Pearson, Mike Hanson, Betty Kovacs, Richard Weil, Xavier Pi-Sunyer, Steven Feldon, William Fisher, Dorothea Castillo, Valerie Davis, Lourdes Fagan, Rachel Hollar, Tammy Keenan, Peter MacDowell, John Keltner, Kim Plumb, Laura Leming, John S Werner, Danielle Harvey, Chris Johnson, John Keltner, John S Werner, Kim Plumb, Laura Leming, Jan Bausch, Shan Gao, Xin Tu, Hua He, Arthur Watts, Debbie Baker, Radu Constantinescu, Karen Helles, Nichole McMullen, Bev Olsen, Larry Preston, Victoria Snively, Ann Stoutenburg, Deborah Friedman, O Iyore Ayanru, Elizabeth-Ann Moss, Pravin Patel, Richard Mills, Maureen Maguire, William Hart Jr, Joanne Katz, David Kaufman, Cynthia McCarthy, John Selhorst, Kathleen Digre, James Corbett, Neil R Miller, Richard Mills

Abstract

Purpose: The Idiopathic Intracranial Hypertension Treatment Trial (IIHTT) showed that acetazolamide provided a modest, significant improvement in mean deviation (MD). Here, we further analyze visual field changes over the 6-month study period.

Methods: Of 165 subjects with mild visual loss in the IIHTT, 125 had perimetry at baseline and 6 months. We evaluated pointwise linear regression of visual sensitivity versus time to classify test locations in the worst MD (study) eye as improving or not; pointwise changes from baseline to month 6 in decibels; and clinical consensus of change from baseline to 6 months.

Results: The average study eye had 36 of 52 test locations with improving sensitivity over 6 months using pointwise linear regression, but differences between the acetazolamide and placebo groups were not significant. Pointwise results mostly improved in both treatment groups with the magnitude of the mean change within groups greatest and statistically significant around the blind spot and the nasal area, especially in the acetazolamide group. The consensus classification of visual field change from baseline to 6 months in the study eye yielded percentages (acetazolamide, placebo) of 7.2% and 17.5% worse, 35.1% and 31.7% with no change, and 56.1% and 50.8% improved; group differences were not statistically significant.

Conclusions: In the IIHTT, compared to the placebo group, the acetazolamide group had a significant pointwise improvement in visual field function, particularly in the nasal and pericecal areas; the latter is likely due to reduction in blind spot size related to improvement in papilledema. (ClinicalTrials.gov number, NCT01003639.).

Figures

Figure 1
Figure 1
Mean threshold change in dB from baseline to 6 months at each test location within each treatment group, with positive values indicating improvement with the treatment failure subjects included. Note that the greatest changes occurred in the periphery and around the blind spot but improvement occurred across the visual field. Green: 2 dB or more improvement. Yellow: 1–2 dB improvement. Red: less than 1 dB improvement.
Figure 2
Figure 2
(A) Magnitude of treatment effect (acetazolamide–placebo) at each test location. (B) Value for statistical significance of the treatment effect at each test location; P < 0.05 shown in darker green.
Figure 3
Figure 3
Mean threshold changes (dB) from baseline to 6 months within each treatment group by zone; the zones are described in Supplementary Figure S1. The acetazolamide treatment group is represented by the dashed line and the placebo group is represented by the solid line. Error bars denote one standard error. Zones of increasing eccentricity are shown on the left and the pericecal zone adjacent to the blind spot is shown on the far right.
Figure 4
Figure 4
Percentages of subjects with a positive slope (estimated using PLR) at each test location by treatment group. Results for acetazolamide are shown on the left and those for placebo on the right. Note that the group differences are minor. Treatment failure subjects did not have enough visual field examinations to be included in these analyses.
Figure 5
Figure 5
Schematic of the visual island of a right eye in IIH modelling damage due to high- and low-grade papilledema. Blue lines represent the profile of the normal visual island through the horizontal meridian. Green dotted line: represents visual loss in the eye with low-grade papilledema. Red dashed line: the visual loss in the eye with high grade papilledema. The x-axis numbers are degrees of visual field eccentricity for a right eye.

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Source: PubMed

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