Patients with herpes zoster ophthalmicus are more than 4 times likely to develop corneal ulcers as individuals without the condition, according to a new population-based cohort study.

The researchers, led by Shih-Feng Weng of Kaohsiung Medical University in Taiwan, analyzed data from Taiwan’s National Health Insurance Research Database. Specifically, they tracked 44,317 newly diagnosed herpes zoster ophthalmicus (HZO) patients and 132,951-matched controls between January 2004 and December 2011, with follow-up through the end of 2013. 

Controls were matched on age, sex, and index date, and all subjects were negative for prior corneal ulcer diagnoses at study entry. Comorbidities—including diabetes mellitus, chronic renal disease, atopy traits, HIV infection, and ocular allergic conditions—were accounted for in multivariate analyses.

The investigators found that incidence rate of corneal ulcer was 53.55 per 10,000 person-years (PY) in HZO patients compared with 11.65 per 10,000 PY in controls, while incidence rate ratio (IRR) was 4.59 (95% confidence interval [CI] = 4.23–4.99, P<.0001). The adjusted hazard ratio (HR) for corneal ulcer in HZO patients was 4.53 (95% CI = 4.17–4.93, P<.05), even after adjusting for all major confounders.

The highest incidence (72.83 per 10,000 PY) was observed in patients ages 12 to 19. Patients with HZO who were age 80 and older had a 12.15-fold higher risk than controls of the same age group.

IRR for men was 5.44 (95% CI = 4.83–6.14) vs 3.90 (95% CI = 3.48–4.38) for women.

Contact lens wearers with HZO had the highest ulcer incidence of 1,000 per 10,000 PY. Even after adjustment, contact lens wear remained a strong independent risk factor (adjusted HR = 13.82, 95% CI = 1.95–98.16).

HZO patients with comorbid ocular allergic conditions had a rate of 87.12 per 10,000 PY (IRR = 4.88, 95% CI = 2.54–9.38). Diabetes and chronic renal disease in HZO patients were also associated with significantly increased ulcer risk (IRR = 4.77 and 5.89, respectively).

The researchers attributed the increased ulcer risk in HZO to multiple pathophysiological mechanisms, including:

• Exposure keratopathy resulting from cicatricial eyelid changes (e.g., entropion, trichiasis, lagophthalmos)
• Neurotrophic keratopathy leading to reduced corneal sensation and blinking
• Secondary infections due to disrupted epithelium, compounded by use of topical corticosteroids, immunomodulatory eye drops, and systemic immunosuppressants

In young adults, behaviors such as poor contact lens hygiene and frequent eye rubbing were cited as additional contributors.

The researchers also noted that cumulative incidence of corneal ulcers was significantly higher in HZO patients throughout the follow-up period (log-rank P<.0001), and their findings established HZO as an independent and significant risk factor for corneal ulceration, particularly in adolescents and young adults (12 to 29 years), patients with ocular allergic conditions, and contact lens wearers.

The authors recommend proactive monitoring of corneal integrity in HZO patients, especially in those who have coexisting risk factors. Counseling regarding exposure keratopathy, neurotrophic complications, and the risks of immunosuppressive treatments may help mitigate long-term vision-threatening complications, the authors add.

The authors reported no conflicts of interest.

Source: Frontiers in Medicine