Increasing hospitalisation of patients with herpes zoster ophthalmicus—an interdisciplinary retrospective analysis

**Background:** The incidence of herpes zoster (HZ) is rising globally, driven by population aging and increasing numbers of immunocompromised patients. Herpes zoster ophthalmicus (HZO), involving the ophthalmic division of the trigeminal nerve, can lead to severe ocular complications such as keratitis, uveitis, glaucoma, optic neuropathy, and acute retinal necrosis. Prompt antiviral therapy and close monitoring are essential. In Germany, guideline revisions in 2016/2019 recommended intravenous (i.v.) acyclovir for HZ in the head and neck region, including HZO, based on expert consensus. This study aimed to assess the burden of HZ and HZO at a single academic medical center over 13 years.

**Methods:** This retrospective analysis included all patients treated for HZ (ICD-10 codes B02.0–B02.9) at the Department of Dermatology and the Eye Centre of the University Medical Centre Freiburg from January 1, 2009, to December 31, 2022. Data from 3034 cases were extracted, including ICD-10 code, year, sex, age, treatment site (dermatology, ophthalmology, or both), and postal code. Statistical analyses were performed using R software version 4.2.3, with p-values <0.05 considered significant. Linear regression was used to project future HZO cases.

**Key Results:** Over the 13-year period, the total number of HZ patients increased by 200%. Of the 3034 patients, 1879 were treated in dermatology, 920 in the eye centre, and 235 in both departments. The median age was 64 years (Q1: 49, Q3: 76), with more females (1586) than males (1448). Women had a higher median age (66 years) than men (63 years). The increase was primarily driven by HZO cases, which showed an approximately eightfold rise in inpatient admissions at the eye centre. In contrast, dermatology inpatient numbers remained stable, and outpatient HZO cases decreased. The proportion of HZO patients per year increased significantly (p<0.05). HZO patients had a higher mean age (66 years) than those with HZ at other sites. The increase in HZO was observed across all age groups (0–40, 40–59, 60–79, and ≥80 years; p<0.05), with the highest number in the 60–79 age group. For HZ at other sites, numbers remained relatively constant, with a slight increase in age groups 0–40, 40–59, and ≥80 years (p<0.05), but a decline in the 60–79 age group since 2018 (p<0.05). Linear regression of HZO cases per year showed a highly significant correlation (p<0.05) with an R² of 0.9016. Assuming constant growth, HZO cases are projected to double by 2040.

**Clinical Implications:** The rising incidence of HZO, particularly in older adults, poses a growing challenge for healthcare systems. The increase in inpatient HZO cases is likely influenced by guideline recommendations for i.v. acyclovir, but the trend predates these guidelines, suggesting a real increase. The aging population and potential effects of varicella vaccination on exogenous boosting may contribute. Despite the availability of an effective inactivated HZ vaccine (Shingrix) since 2018, vaccination rates in Germany remain low (11.5% initial, 7.7% fully vaccinated), limiting its impact. Higher vaccination coverage could prevent a substantial proportion of HZ cases in older adults. The projected doubling of HZO hospitalizations by 2040 underscores the need for increased inpatient ophthalmological capacity and consideration of alternative treatments, such as oral valacyclovir, which may reduce hospitalization rates if proven equally effective. Future studies should assess vaccination status, vitamin D levels, and immunosuppressive factors to better understand the drivers of HZO.