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e16237 Background: Alcohol use (AU) and Liver cell carcinoma (LCC) are significant contributors to adult mortality worldwide. Examining trends and disparities in AU and LCC-related deaths is essential for understanding public health challenges and formulating targeted interventions. This study investigates national mortality patterns related to AU and LCC in the United States from 1999 to 2023, emphasizing demographic, geographic, and temporal disparities. Methods: This descriptive analysis used the CDC WONDER database (1999–2023) to identify AU-related deaths (ICD-10 codes E24.4, F10, G32.2, G62.1, G72.1, I42.6, K70, K85.2, K86.0, R78.0, T51, X65, Y15) and LCC (ICD-10 code C22.0) in adults aged 25 and older. Age-adjusted mortality rates (AAMRs) per 1,000,000 individuals were calculated, stratified by gender, race/ethnicity, census region, urban-rural classification, and state. Trends were analyzed using Joinpoint regression to compute annual percent changes (APCs) and 95% confidence intervals (CIs). Statistical significance was set at p < 0.05, and analyses adhered to STROBE guidelines. Results: From 1999 to 2023, a total of 21,007 deaths were attributed to LCC and AU (Men: 18,836 Women: 2,171). AAMRs showed a stable trend from 1999 to 2003 (APC: 0.0; 95% CI: -8.7 to 4.9) but increased significantly from 2003 to 2019 (APC: 6.1; 95% CI: 5.7 to 7.4), stabilizing from 2019 to 2023 (APC: -0.6; 95% CI: -3.2 to 1.3). Men's AAMRs decreased from 1999 to 2003 (APC: -1.1; 95% CI: -10.4 to 3.4), then rose sharply from 2003 to 2019 (APC: 6.1; 95% CI: 5.6 to 7.1). For women, AAMRs increased significantly, particularly between 2013 and 2017 (APC: 12.4; 95% CI: -9.5 to 25.1). Non-Hispanic Black and White populations experienced notable increases in AAMRs, while Hispanic people showed an initial decline followed by an increase post-2004 (APC: 4.7; 95% CI: 3.7 to 7.9). The West had the highest regional AAMR (5.3; 95% CI: 5.2 to 5.5), while the Northeast recorded the lowest (2.1; 95% CI: 2.0 to 2.2). New Mexico had the highest state AAMR (8.4; 95% CI: 7.4 to 9.4), and Mississippi the lowest (1.2; 95% CI: 0.9 to 1.5). AAMRs rose more sharply in non-metropolitan areas from 1999-2020 (APC: 6.6; 95% CI: 5.9 to 7.8) compared to metropolitan regions from 2004 to 2020 (APC: 5.4; 95% CI: 4.9 to 6.5). Conclusions: AU and LCC-related mortality rates have increased significantly since 2003, with distinct gender, racial, and geographic disparities. Men and rural populations faced higher mortality increases, with notable variations across states and regions. These findings underscore the need for focused public health efforts to mitigate these disparities and address the growing burden of LCC and AU-related mortality.

e16456 Background: Gastric cancer is one of the significant contributors of mortality and morbidity, especially in older patients. Analyzing national trends in the Disability adjust life years (DALY) helps identify the evolving burden of this disease among patients older than 70 years and highlights the regions requiring particular interventions. Methods: Using Global burden of disease data from 2021, national DALY rates per 100,000 people aged 70 and over with gastric cancer were assessed. The Estimated Annual Percentage Change (EAPCs) with p value taken as a statistical measure of significance, was used to evaluate trends from 1990 to 2021. Results: The analysis displays considerable contrasts in the trends of gastric cancer burden across nations. From 1990 to 2021, a rising trend in DALY EAPC was seen in Egypt (1.01883; 95% CI: -0.1931- 1.958) followed by Honduras (0.3262; 95% CI: 0.0177- 0.7456) and Lesotho (0.2253; 95% CI:-0.1326- 0.6995). Conversely, Austria (-0.7368; 95% CI: -0.7646 to -0.7087), Republic of Korea (-0.7095; 95% CI: -0.7620 to -0.6442) and Singapore (-0.6923; 95% CI: -0.7286 to -0.6553) reported a prominent decline in DALY EAPCs, reflecting significant progress in reducing burden. The DALY rates in 2021 also varied dramatically among nations. Highest DALY rate was observed in Bolivia (4882.7; 95% CI:3782.9- 6349.7) underscoring highest impact on healthcare system. Conversely, Morocco (329.69; 95% CI: 234.64- 410.12) recorded lowest DALY rate indicating comparatively better disease control or lower incidence. Conclusions: While some nations demonstrate remarkable progress in mitigating the burden of gastric cancer, others still face significant challenges. Highest increase in EAPC in Egypt, Honduras and Lesotho whereas significant decline in Austria, Korea, and Singapore indicates areas of target public health efforts. Future research should focus on understanding the causes of these disparities and evaluating the impact of interventions across it. DALY and EPAC. Country 2021 DALY rate EAPC(1990-2021) EAPC, 95% CI Egypt 1272.146 1.018834(highest) -0.193 to 1.959 Honduras 2880.563 0.32617 0.018 to 0.746 Lesotho 1555.79 0.225384 -0.133 to 0.699 Singapore 806.6098 -0.692396 -0.729 to -0.655 Republic of Korea 1961.151 -0.709502 -0.762 to -0.644 Austria 662.5105 -0.736826(lowest) -0.765 to -0.709 Morocco 410.1227(lowest) -0.17817 -0.387 to 0.097 Bolivia 4882.718(highest) -0.32185 -0.473 to -0.103

e16423 Background: Pancreatic cancer (PC) is one of the most aggressive malignancies, disproportionately affecting older adults. Leveraging data from the Global Burden of Disease (GBD), this study investigates gender-specific trends in disability-adjusted life years (DALYs) and mortality rates for PC among adults aged 70 and older from 1990 to 2021. Methods: DALYs and mortality rates associated with PC were extracted for both genders from the GBD-2021 study from 1990 to 2021. The Annual Percentage Change (APC) and the Average Annual Percentage Change (AAPC) were calculated, along with 95% confidence intervals (CI), to assess the statistical significance of the trends using the p-value. Results: In 1990, DALY rates were 837.25 for men and 711.95 for women, increasing to 950.68 and 768.31, respectively, by 2021. Mortality rates followed a similar pattern: men’s rates rose from 52.05 in 1990 to 61.37 in 2021, while women’s increased from 47.31 to 53.40. Men consistently experienced higher burdens than women. The AAPC analysis revealed that men exhibited a steeper rise in both DALYs and mortality rates associated with PC compared to women over the past three decades. Notably, the gender disparity was more evident in DALYs (+0.1929%) than in mortality rates (+0.1358%), with all AAPC values demonstrating statistical significance (p < 0.000001). Following the APC analysis, additional significant trends were identified. Among males, DALY rates demonstrated the most pronounced increase between 1997 and 2021 (APC: 0.5397, 95% CI: 0.5118, 0.5645), whereas in females, the most significant rise occurred from 1990 to 1993 (APC: 0.6593, 95% CI: 0.3608, 1.1016). Conversely, the slowest increase in DALY rates among females was observed between 1993 and 2003 (APC: 0.0925, 95% CI: -0.2053, 0.1641). For mortality rates, the most notable rise in males was observed between 2007 and 2010 (APC: 1.2314, 95% CI: 1.0292, 1.3195), while females experienced their sharpest escalation from 1990 to 1994 (APC: 0.6891, 95% CI: 0.4322, 1.0720). In contrast, the slowest rate of progression in mortality among females occurred between 1993 and 2002 (APC: 0.1736, 95% CI: 0.0180, 0.2368). Conclusions: Over the past three decades, men have experienced a significantly more pronounced rise in DALYs and mortality rates related to PC compared to women.These findings highlight the urgent need for gender-specific interventions to address the growing burden of PC in aging populations. Trends in DALY and mortality rates per 100,000 by gender (1990-2021). Metrics Gender 1990 2021 APC (1990-2021) Daly Rates per 100,000 Male 837.25 950.68 0.4422 Female 711.9 768.31 0.2493 Mortality Rates per 100,000 Male 52.05 61.37 0.5366 Female 47.31 53.40 0.4008

e16420 Background: Pancreatic cancer (PC) typically follows an indolent course and is often diagnosed at an advanced stage, contributing to its high mortality rate, particularly among older adults. Its aggressive nature makes it a significant global health burden, causing substantial mortality across nations. This analysis investigates national mortality trends in adults aged 70 years and older from 1990 to 2021, utilizing data from the Global Burden of Disease (GBD) Study. Methods: We utilized data from the GBD-Study 2021 to report the number of cases and age-standardized rates (per 100,000 population) of PC. To assess mortality trends from 1990 to 2021, we calculated the estimated annual percentage change (EAPC) along with corresponding 95%confidence intervals (CI), providing a robust evaluation of temporal patterns. Results: Over the past three decades, deaths attributable to PC have shown a significant increase globally. In 1990, the United States of America (USA) reported the highest number of PC-related deaths, followed by China and Japan. By 2021, however, China surpassed the USA, becoming the leading contributor to PC mortality, with Japan maintaining its position as the third highest.In 2021, the United Arab Emirates reported the highest mortality rate (148.15), which was more than double its 1990 rate (70.71). The Principality of Monaco (140.87) and Uruguay (129.39) held the second and third highest mortality rates, respectively. The lowest mortality rates were recorded in Mozambique (8.18), Malawi (8.98), and Sao Tome and Principe (9.01).Countries with the largest increases in the EAPC included Turkmenistan (EAPC: 15.16, 95% CI: 10.92, 21.02), Republic of Cabo Verde (EAPC: 13.60, 95% CI: 8.56, 19.48), and Mongolia (EAPC: 4.80, 95% CI: 3.11, 7.26). In contrast, the greatest declines were observed in the Republic of San Marino (EAPC: -0.32, 95% CI: -0.52, -0.07), Guam (EAPC: -0.27, 95% CI: -0.41, -0.13), and Greenland (EAPC: -0.24, 95% CI: -0.44, 0.007). Conclusions: Globally, mortality rates associated with PC among individuals aged 70 and older increased from 1990 to 2021, with particularly notable rises in Turkmenistan, Republic of Cabo Verde, and Mongolia. These findings underscore the critical need for enhanced prevention strategies, improved management, and research to address underlying disparities. Mortality percent change. Metric Region 1990 2021 EAPC with 95% CI (1990-2021) Highest mortality percent change Turkmenistan 1.19 19.34 15.16 (10.92, 21.02) Republic of Cabo Verde 6.47 94.55 13.60 (8.56, 19.48) Mongolia 10.21 59.24 4.80 (3.11, 7.26) Lowest mortality percent change Republic of San Marino 89.48 60.47 -0.32 (-0.52, -0.07) Guam 32.46 23.51 -0.27 (-0.41, -0.13) Greenland 169.52 127.96 -0.24 (-0.44, 0.007)

e16419 Background: Pancreatic cancer remains one of the most lethal malignancies worldwide. While high-income regions have long faced higher rates, recent trends show that lower-income regions are also beginning to see an increase. This study explores how pancreatic cancer incidence and prevalence have changed over the past 30 years among adults aged 70 and older assessing regional differences. Methods: We analyzed data from the Global Burden of Disease (GBD) spanning three decades (1990–2021) to assess pancreatic cancer incidence and prevalence rates among adults aged 70+. Data focused on different regions worldwide, grouping them by income levels using the Socio-demographic Index (SDI) and annual changes in incidence and prevalence rates were calculated. Results: In 2021, High-income Asia Pacific had the highest incidence rate at 119.52 per 100,000, whereas Low SDI regions had the lowest at 12.01 per 100,000. High-income regions accounted for the majority of cases, with over 140,000 reported, compared to fewer than 3,000 in the lowest-income areas. Andean Latin America experienced significant APC fluctuations, with a sharp rise from 2015 to 2019 followed by a decline, while High-income North America saw a recent decrease in incidence. Overall, most regions exhibit a steady increase in pancreatic cancer prevalence, with higher AAPCs in Sub-Saharan Africa, North Africa, and parts of Asia, while high-income regions show more moderate increases. Trend analysis reveals significant trends in pancreatic cancer incidence and prevalence among individuals aged 70+. Western Sub-Saharan Africa has the highest Average Annual Percent Change (AAPC) at 2.3248%, indicating the most substantial increase in prevalence from 1990 to 2021, followed by North Africa and the Middle East at 1.9906%. Low-middle SDI regions also show a steady rise with an AAPC of 1.718%, while high-income regions like High-income Asia Pacific report a notable AAPC of 1.595%. Conclusions: Our findings show a concerning rise in pancreatic cancer among older adults, with the most dramatic increases in regions like Western Sub-Saharan Africa and North Africa. To tackle this growing challenge, we need focused efforts on prevention, early detection, and accessible care, especially in lower-resource settings. Incidence percent changes. Metric Region 1990 2021 AAPC (1990-2021) Highest incidence percent change Western Sub-Saharan Africa 7.62 15.38 2.31 North Africa and Middle East 20.97 37.23 1.91 Lowest incidence percent change Caribbean 41.51 41.36 -0.016 Southern Latin America 74.05 73.89 0.006 Highest prevalence percent change Western Sub-Saharan Africa 4.54 9.21 2.32 North Africa and Middle East 12.49 22.77 1.99 Lowest prevalence rate percent change Caribbean 25.02 25.38 0.02 Southern Latin America 44.78 45.45 0.06

e16418 Background: Pancreatic cancer remains one of the most fatal malignancies globally, posing a significant burden on older populations. Despite numerous reports on its prevalence, a detailed comparative analysis of national trends among adults aged 70 and older from 1990 to 2021 is scarce. This study seeks to bridge this gap by evaluating prevalence rates using data from the Global Burden of Disease (GBD) study. Methods: Prevalence data for pancreatic cancer in individuals aged 70 years and older were obtained from the GBD-2021 dataset, encompassing 204 countries and territories for the years 1990 and 2021. The Estimated Annual Percent Change (EAPC) and corresponding 95% confidence intervals (CI) were calculated to assess trends over the period from 1990 to 2021. Results: The prevalence of pancreatic cancer has shown a significant increase since 1990, reaching its highest levels in 2021. In 1990, the United States of America (USA) reported the highest prevalence, followed by Japan and China. However, by 2021, Japan ranked first in prevalence, followed by China and the USA. The analysis revealed that in 1990, the highest prevalence rates of pancreatic cancer were observed in Greenland (91.04 per 100,000), followed by Finland (82.57 per 100,000) and Japan (76.30 per 100,000). By 2021, Japan reported the highest prevalence (126.73 per 100,000), followed by Finland (119.20 per 100,000) and Canada (109.22 per 100,000). Despite the observed prevalence rates from 1990 to 2021, Turkmenistan exhibited the most significant increase (EAPC: 15.41, 95% CI: 10.91, 21.41), followed by the Republic of Cabo Verde (EAPC: 13.61, 95% CI: 8.67, 19.59) and Mongolia (EAPC: 4.81, 95% CI: 3.11, 7.20). In contrast, the most significant declines were recorded in the Republic of San Marino (EAPC: -0.308, 95% CI: -0.51, -0.03), followed by Guam (EAPC: -0.24, 95% CI: -0.37, -0.08) and Cuba (EAPC: -0.21, 95% CI: -0.33, -0.09). Conclusions: The prevalence of pancreatic cancer among adults aged 70 and older has increased significantly over the past three decades, with distinct regional patterns. Countries like Japan, China, and the USA continue to report the highest prevalence rates. These findings highlight the urgent need for targeted prevention, screening, and treatment strategies, particularly in high-burden regions, to mitigate the growing impact of pancreatic cancer in aging populations. Prevalence percent changes. Metric Region 1990 2021 EAPC with 95% CI (1990-2021) Highest prevalence percent change Turkmenistan 0.62 10.16 15.41 (10.91, 21.41) Republic of Cabo Verde 3.23 47.18 13.61 (8.67, 19.59) Mongolia 5.25 30.53 4.81 (3.11, 7.20) Lowest prevalence percent change Republic of San Marino 52.61 36.36 -0.308 (-0.51, -0.03) Guam 16.96 12.87 -0.24 (-0.37, -0.08) Cuba 32.65 25.52 -0.21 (-0.33, -0.09)

e16481 Background: Gastric cancer is a malignant disease characterized by the uncontrolled growth of cells in the stomach lining. It is a global health concern with regional variation in incidence and prevalence. This study investigates the regional incidence and prevalence of gastric cancer among adults aged 70 and older from 1990 to 2021, utilizing data from 26 global regions. Methods: Global Burden of Disease (GBD) data for 2021 were analyzed to assess regional incidence and prevalence of gastric cancer among adults aged ≥ 70. The Annual Average Percentage Change (AAPC) was calculated to evaluate trends from 1990 to 2021, with statistical significance determined using p-values. Results: In 2021, East Asia has the highest incidence (273403) followed by Middle SDI (189383) and High-middle SDI (176691). Highest Prevalence numbers were recorded for East Asia (398,000) followed by High SDI (337,000) and High-middle SDI (250,000). With regards to rates per 100,000, Oceania has the lowest incidence (257) as well as prevalence (252) followed by Central Sub-Saharan Africa (I:1142 , P: 1081) and Southern Sub-Saharan Africa (I:1295, P: 1227). The largest increase in AAPC of incidence was exhibited by Western Sub Saharan Africa (-0.24, CI: -0.27 to -0.23), Southern Sub Saharan Africa (-0.29, CI: 0.37 to -0.22), and South Asia (-0.306, CI: -0.422 to -0.158) regions, while South Asia (-0.087, CI: -0.1748 to 0.0308), East Asia (-0.0952, CI: 0.0284 to 0.1606), and Andean Latin America (-0.1696, CI: -0.3498 to -0.0381) showed largest increase in AAPC of prevalence. Western Europe region had the greatest decline in AAPC of incidence (-2.3995, CI: -2.4374 to -2.3691) followed by Central Europe (-2.2010, CI: -2.3007 to -2.1445) and Eastern Europe (-2.1554, CI: -2.212 to -2.0925 ) regions while Central Asia had the greatest decline in AAPC of prevalence (-1.9281, CI: -2.0109 to -1.8522) followed by High Income Asia Pacific (-1.8268, CI: -1.8926 to -1.7913) and Eastern Europe (-1.8103, CI: -1.8631 to -1.7623). All AAPC values were statistically significant (p < 0.000001). Conclusions: The East Asia region exhibited the highest incidence and prevalence, highlighting the vulnerability of these populations, while Central Sub-Saharan Africa bore the least burden. Notably, several regions, particularly in Asia, experienced substantial increases in both incidence and prevalence, emphasizing the need for targeted interventions. Conversely, some regions, such as Europe, showed encouraging declines in prevalence, suggesting that effective prevention and control strategies can be implemented. These findings underscore the importance of tailored approaches to address the evolving burden of Gastric Cancer.

e22572 Background: Pancreatic cancer is a highly lethal malignancy that disproportionately impacts older populations, contributing significantly to global disease burden. Disability-adjusted life years (DALY) serve as a comprehensive metric to quantify the combined impact of mortality and morbidity. This analysis of the Global Burden of Disease Study-2021 (GBD-2021) aims to characterize trends in DALY rates attributable to pancreatic cancer among individuals aged 70 years and older across 204 nations. Methods: Data on DALY associated with pancreatic cancer for individuals aged 70+ were extracted for 204 nations from the GBD-2021 study for the years 1990 and 2021. Estimated annual percent change (EAPC) with 95% confidence intervals (CI) were calculated from 1990 to 2021. Results: The DALY rates were accessed among individuals aged 75 and older diagnosed with pancreatic cancer. In 1990, Greenland exhibited the highest DALY rate globally (2825.65), but by 2021, this position was surpassed by the United Arab Emirates (2775.52), with Greenland declining to the second-highest rate (2082.43). On the other hand, Turkmenistan had the lowest DALY rates in 1990, but by 2021, Mozambique had taken this position, with Turkmenistan ranking 170th. Despite the observed DALY rates from 1990 to 2021, Turkmenistan experienced the highest change (EAPC: 15.23, 95% CI: 10.88–21.18), followed by the Republic of Cabo Verde (EAPC: 12.88, 95% CI: 8.14–18.75) and Mongolia (EAPC: 4.53, 95% CI: 2.90–6.88). A decrease in DALY was observed in over 24 nations, with the Republic of San Marino recording the largest decline (EAPC: -0.37, 95% CI: -0.55, -0.12), followed by Bermuda (EAPC: -0.26, 95% CI: -0.43, 0.03) and Greenland (EAPC: -0.26, 95% CI: -0.45, -0.009). Conclusions: From 1990 to 2021, DALY rates related to pancreatic cancer among individuals aged 70 and older rose worldwide, particularly in Turkmenistan, the Republic of Cabo Verde, and Mongolia. There is a pressing need for global adoption of screening programs to enable early detection and treatment of these cases. Metric Region 1990 2021 EAPC with 95% CI (1990-2021) HIGHEST DISABILITY-ADJUSTED LIFE YEARS (DALYS) PERCENT CHANGE Turkmenistan 19.66 319.09 15.22 (10.88–21.18) Republic of Cabo Verde 98.12 1361.76 12.88 (8.14–18.75) Mongolia 172.14 952.05 4.53 (2.90–6.88) LOWEST DISABILITY-ADJUSTED LIFE YEARS (DALYS) PERCENT CHANGE Republic of San Marino 1323.96 834.01 -0.37 (-0.55, -0.12) Bermuda 1696.97 1249.11 -0.26 (-0.43, 0.03) Greenland 2825.66 2082.43 -0.26 (-0.45, -0.009)

e22570 Background: Aging into the seventh decade of life marks a pivotal shift in cancer susceptibility, with pancreatic cancer (PC) emerging as one of the most relentless threats to global health. This study utilizes three decades of Global Burden of Disease (GBD) data to unravel unprecedented insights into the prevalence and incidence of PC among adults aged 70 and older. Methods: We analyzed data from the GBD study to assess the temporal trends in the incidence and prevalence of PC from 1990 to 2021. The Annual Percentage Change (APC) and Average Annual Percentage Change (AAPC), along with 95% confidence intervals (CI), were utilized to assess the overall trends, with statistical significance evaluated using p-values. Results: Over the past three decades, the global burden of PC has surged significantly. In 1990, the global incidence of PC stood at 45.12 per 100,000, escalating to 54.47 per 100,000 by 2021. Likewise, global prevalence increased from 30.33 per 100,000 in 1990 to 40.60 per 100,000 in 2021, with incidence rates consistently exceeding prevalence, suggesting an accelerating number of new cases of PC worldwide. The AAPC analysis revealed a significant upward trajectory in both global incidence (AAPC: 0.6085, 95% CI: 0.5801, 0.6273 p < 0.000001) and prevalence (AAPC: 0.9467, 95% CI: 0.9188, 0.9659 p < 0.000001) of PC. Following the APC analysis, several notable trends emerged. The global incidence of PC experienced its most substantial increase between 2003 and 2010 (APC: 1.0806, 95% CI: 0.9817, 1.3206 p < 0.000001), while the slowest growth in incidence occurred from 1990 to 2003 (APC: 95% CI: 0.9817, 1.3206 p = 0.000400). Conversely, the global prevalence of pancreatic cancer saw its most pronounced rise between 1998 and 2001 (APC: 2.0389, 95% CI: 1.2005, 2.1962 p < 0.000001), with the slowest increase occurring from 1994 to 1998 (APC: 0.4632, 95% CI: 0.2544, 1.9767 p = 0.001200). Conclusions: The persistent rise in both incidence and prevalence of PC over the past three decades underscores a critical global health challenge, with a marked acceleration in recent years. These findings highlight the urgent need for targeted interventions and a deeper understanding of the factors driving this expanding burden, particularly as the incidence consistently outpaces prevalence. Metric Overall 1990 2021 AAPC with 95% CI (1990-2021) INCIDENCE RATES PER 100,000 Global Incidence 45.12 54.47 0.61 (0.58, 0.63) PREVALENCE RATES PER 100,000 Global Prevalence 30.33 40.60 0.95 (0.92, 0.97)

Importance High-quality evidence regarding suppressive valacyclovir treatment in herpes zoster ophthalmicus (HZO) is necessary to guide care. Objective To determine whether suppressive valacyclovir compared with placebo delays the occurrence of new or worsening stromal keratitis (SK), endothelial keratitis (EK), iritis, or dendriform epithelial keratitis (DEK) during 12 months of treatment and if treatment benefit persisted at 18 months (secondary end point). Design, Setting, and Participants The Zoster Eye Disease Study (ZEDS) was a randomized clinical trial conducted in 95 sites from November 2017 to June 2024. Immunocompetent, nonpregnant adults with a history of an HZO rash, documented active keratitis or iritis within 1 year, and an estimated glomerular filtration rate of 45 mL/min/1.73 m 2 or greater were eligible. After determined to be eligible, participants were randomized in 4 strata: age at onset (&amp;lt;60 years vs ≥60 years) and disease duration (&amp;lt;6 months vs ≥6 months). Interventions A total of 12 months of double-masked daily valacyclovir, 1000 mg, or placebo. Main Outcomes and Measures The primary outcome was time to first occurrence within 12 months of new or worsening SK, EK, iritis, or DEK. Results A total of 527 participants (median [IQR] age, 60 [50-68] years; 266 female [50.5%]; 266 in the valacyclovir group; 261 in the placebo group) were randomized in 4 strata; 481 completed 12 months, and 460 completed 18 months. Data were analyzed by intention to treat. At 12 months, primary end points occurred in 86 participants (33%) assigned to placebo and 74 (28%) assigned to valacyclovir, and at 18 months in 104 participants (40%) assigned to placebo and 86 (32%) assigned to valacyclovir. The hazard ratio (HR) of the primary end point at 12 months was 0.77 for participants taking valacyclovir vs placebo (HR, 0.77; adjusted 95% CI, 0.56-1.05; P = .09) and 0.73 at the secondary end point at 18 months (HR, 0.73; adjusted 95% CI, 0.55-0.97; P = .03). There was a reduction of multiple other secondary end points at 12 months (HR, 0.70; 95% CI, 0.52-0.95; P = .02) and 18 months (HR, 0.72; 95% CI, 0.55-0.95; P = .02). Conclusions and Relevance Although the primary outcome did not show a benefit of suppressive valacyclovir treatment, secondary study outcomes showed treatment superiority at the 18-month end point and reduced number of multiple episodes of keratitis or iritis at both 12 and 18 months. These results support consideration of 1 year of suppressive valacyclovir treatment for HZO. Trial Registration ClinicalTrials.gov Identifier: NCT03134196