Citations 2
Low-Dose Valacyclovir for Postherpetic Neuralgia in the Zoster Eye Disease Study
Warner, David, Jeng, Bennie H., Kim, Jiyu , Liu, Mengling , Baratz, Keith H. , Mian, Shahzad I., Choulakian, Mazen Y., Meyer, Jay J. , Lu, Ying , Twi-Yeboah, Alberta , Lopez-Jimenez, Carlos, Laury, Sarah, Cohen, Elisabeth J. , Weissbart, Sarah B. , Abazari, Azin, Chou, Timothy , Chang, Eileen , Amescua, Guillermo , Koo, Ellen, Galor, Anat , Berestka, John S., Nanji, Afshan, Stutzman, Richard D., Clements, John, Davies, Emma , Saeed, Hajirah N. , Ciralsky, Jessica, Fernández, A. Gómez-Bastero , Sippel, Kimberly C. , Perez-Quinones, Victor L, Daluvoy, Melissa B. , Liu, Katy C., Ewald, M., Groos, Erich B, Chang, Bernard, Shivitz, Ira A., Hill, Jordan , Fowler, Priscilla G., Read, Russell W. , Geggel, Harry S. , Rony, Sayegh, Rapuano, Christopher J. , Meghpara, Beeran, Holland, Gary N. , Irvine, John, Aldave, Anthony J. , Edmund, Tsui, Chen, Judy , Honig, Marc A, Snyder, Lee A, Lubniewski, Anthony J., Katz, Douglas, Capoor, Seema, Gonzales, John, Morkin, Melina I., Kenyon, Kenneth R., Lee, William B., Christenbury, Joseph, LaMattina, Kara C. , Negahban, Kambiz, Rao, Ronihi, Ament, Christine S, Lopatynsky, Marta O., Barbato, John D, Sarkar, Jayati S, Macsai, Marian S., Herz, Joshua B, Al-Mohtaseb, Zaina , Matoba, Alice Y., Cooney, Theresa, Hood, Christopher , Sugar, Alan M., Shtein, Roni M., Nehls, Sarah, Warner, Evan J. , Nettune, Greg, Bowman, Brad, Gelender, Henry, Alexander, Jamie K. , McCall, Tyrone, Zaffos, Joshua, Beebe, Walter E., Potts, Luke B. , Lustbader, Jay M., Oboh-Weilke, Aruoriwo, Hammersmith, K.M., Orlin, Stephen E., Nagra, Parveen K., Sulewski, Michael E., Bunya, Vatinee Y. , Shafer, Brian M. , Viriya, Elizabeth T., Qureshi, Anam, Lazzaro, Douglas R., Palazzolo, Laura , Goyal, Himani , Schrack, Katie E, Raber, Irving M. , Ayres, Brandon D. , Finklea, Brenton, Reeves, Sherman W., Awad, Omar E, Hardten, David R., Reilly, Charles, Flynn, William J., Rashid, Edward D, Wen, Angie E, Shaik, Neha, Seedor, John A., Rosenfeld, Steven I., Winnick, Marc , Amir, Ahmad, Sherman, Mark D., Chaon, Benjamin, Soukiasian, Sarkis H., Rao, Naveen K. , Steiner, Anne, Winokur, Jules , Udell, Ira J., Shih, Carolyn, Gorski, Matthew , Schrier, Amilia, Lobo-Chan, Ann-Marie , Sugar, Joel, Munir, Wuqaas W, Sunshine, Sarah B. , Miller, Donald M. , Gensheimer, William G. , Zegans, Michael E. , Weiss, Jayne S. , Bernal, M.L. , Barron, Bruce, Hindman, Holly B. , Wise, Ronald E. , Gelston, Christopher D. , Taravella, Michael J. , Davidson, Richard S. , Tran, Uyen, Bartley, Jeremy, McCulley, James P., Verity, Steven M., Bowman, Wayne, Blomquist, Preston H. , Mootha, V. Vinod , Thorne, George, Renucci, A., Verdier, David D. , Sivaraman, K. R., Nordlund, Michael L., Hwang, Frank S. , Affeldt, John, Ingraham, Herbert J., Guibord, Nathalie M, Dobbins, Kendall, Thareja, Tarika , Zaugg, Brian , Mifflin, Mark D., Forstot, S. 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JAMA Ophthalmology | March 6, 2025 | Volume: 143 | Issue: 4 | Pages: 277
10.1001/jamaophthalmol.2024.6113
Importance Evidence regarding suppressive valacyclovir treatment on postherpetic neuralgia is necessary to guide care. Objective To test the hypothesis that suppressive treatment with 1000 mg/d of oral valacyclovir for 12 months reduces the prevalence, severity, and duration of postherpetic neuralgia compared with placebo at 12 and 18 months in participants with herpes zoster ophthalmicus (HZO). Design, Setting, and Participants Multicenter, placebo-controlled randomized clinical trial including 527 immunocompetent, nonpregnant adults with history of HZO rash, documented keratitis, or iritis within 1 year and an estimated glomerular filtration rate of 45 mL/min/1.73 m 2 or greater. The study was conducted at 95 participating sites (in Canada, New Zealand, and the US) from November 2017 to June 2024 and participant visits occurred every 3 months. Intervention Treatment with 1000 mg/d of valacyclovir or placebo for 12 months. Main Outcomes and Measures Prevalence of postherpetic neuralgia, severity as determined by pain score (a score of ≥3 on a scale of 1-10), pain duration (≥3 months after HZO onset), and total daily dose of pain medication. Results Of the 527 participants (490 completed 12 months of treatment and 460 completed 18 months), 73 (14%) had postherpetic neuralgia and were analyzed by age at HZO onset (<60 years or ≥60 years) and disease duration (recent [<6 months] or chronic [≥6 months]). Of the 73 participants with postherpetic neuralgia (34 in the valacyclovir group and 39 in the placebo group), the mean age was 62.4 years (SD, 13.6 years), 59% were female, 5% were Black or African American, and 10% were Hispanic. The prevalence of postherpetic neuralgia at 12 months was not reduced by valacyclovir (12/32 [38%]) compared with placebo (14/35 [40%]) (between-group difference, 2.5% [95% CI, −20.8% to 25.8%]; P >.99). The participants who were younger than 60 years at HZO onset and had a chronic disease duration had lower pain scores in the valacyclovir group (mean score, 0.3 [SD, 0.9]) vs the placebo group (mean score, 0.8 [SD, 1.9]) at 12 months ( P = .045) and at 18 months (mean score, 0.2 [SD, 0.9] vs 1.0 [SD, 2.3], respectively; P = .02). There was a decrease in pain duration in the valacyclovir group at 18 months (mean, 13.6 [SD, 11.4] months) vs the placebo group (mean, 18.7 [SD, 29.5] months) (linear mixed-effects model between-group difference, −3.39 months [95% CI, −6.73 to −0.04 months]; P = .046). The total daily dose of neuropathic pain medication was lower in the valacyclovir group (mean, 271.4 [SD, 593.8] mg/d) vs the placebo group (mean, 363.4 [SD, 592.2] mg/d) at 12 months (linear mixed-effects model P = .006) and at 18 months (mean, 209.0 [SD, 412.8] mg/d vs 286.2 [SD, 577.9] mg/d, respectively; linear mixed-effects model P = .01). Conclusions and Relevance One year of suppressive treatment with valacyclovir was associated with a lower dosage of neuropathic pain medication. Participants in the valacyclovir group, who were younger at HZO onset and had a chronic disease duration, had lower pain scores. These secondary outcomes support consideration of 1 year of suppressive treatment with valacyclovir to reduce dosage of pain medications and pain due to HZO. Trial Registration ClinicalTrials.gov Identifier: NCT03134196
Baseline Participant Characteristics at Enrollment in the Zoster Eye Disease Study
Prescott, Christina R. , Cohen, Elisabeth J. , Lu, Ying , Twi-Yeboah, Alberta , Jiménez, Carlos López , Mazen, Choulakian Y., Warner, David, Baratz, Keith H. , Jeng, Bennie H. , Lu, Ying , Niederer, Rachael L. , Hochman, Judith S. , Troxel, Andrea B. , Mian, Shahzad I.
Cornea | February 27, 2024 | Volume: 43 | Issue: 12 | Pages: 1473-1480
Purpose: The Zoster Eye Disease Study (ZEDS) is the first randomized clinical trial to study the efficacy of long-term (1 year) suppressive valacyclovir treatment on herpes zoster ophthalmicus (HZO) outcomes. This article details the baseline characteristics of participants. Methods: Setting: The study was set at 95 participating clinical centers in 33 states, Canada, and New Zealand. Study Population: Immunocompetent adults with a history of a characteristic HZO unilateral rash and documentation of an episode of active dendriform epithelial keratitis, stromal keratitis, endothelial keratitis, or iritis within the preceding year, enrolled in ZEDS from November 2017 to January 2023. Intervention: Participants were randomized to double-masked oral valacyclovir 1 gm daily versus placebo for 1 year of treatment and followed for 18 months. Results: Five hundred twenty-seven participants were enrolled across 4 strata according to age at HZO onset (younger or older than 60 years) and duration of HZO at enrollment (less or greater than 6 months), with an even distribution of men and women and a median age of 60 years. More participants with recent (57%, 300/527) than chronic HZO and younger than 60 years at HZO onset (54%, 286/527) were enrolled. Most participants were treated acutely with a recommended antiviral regimen (91%, 480/527) and had not been vaccinated against zoster (79%, 418/527). Conclusions: The broad ZEDS study population enhances the likelihood that ZEDS will provide generalizable high-quality evidence regarding the efficacy and safety of suppressive valacyclovir for HZO immunocompetent adults and whether it should become standard of care. Trial Registration: ClinicalTrials.gov Identifier: NCT03134196.