Hutchinson's Sign in Herpes Zoster Ophthalmicus: A Systematic Review and Meta-Analysis.

Abstract

Although traditionally associated with herpes zoster ophthalmicus (HZO), the predictive significance of Hutchinson's sign (HS), or nasociliary nerve involvement, for ocular complications has recently been debated. We conducted a systematic review and meta-analysis to evaluate the association between HS and ocular involvement in HZO. Clinicians across various medical specialties frequently utilize HS to risk-stratify patients presenting with cutaneous signs of HZO, yet recent uncertainty has emerged regarding its clinical value. We searched Ovid MEDLINE, Embase, and Cochrane Library from inception to March 2025 for observational studies reporting on HS in HZO, stratified by the presence of ocular involvement. Paired independent reviewers conducted study screening, data extraction, and risk of bias assessment using the Risk of Bias in Non-randomized Studies of Exposures tool. The primary outcome was the odds ratio (OR) for ocular involvement comparing patients with versus without HS, calculated using a random-effects meta-analysis. The secondary outcomes included pooled sensitivity, specificity, accuracy, positive predictive value (PPV), and negative predictive value (NPV). Fourteen studies (7 retrospective and 7 prospective) were included. Hutchinson's sign was associated with increased odds of ocular involvement compared with the absence of HS (78%, 308/393 in patients with HS vs. 34%, 539/1576 in patients without HS; OR = 6.51, 95% confidence interval = [4.09, 10.34], P < 0.01; 12 studies, 1969 patients, Grading of Recommendations Assessment, Development, and Evaluation [GRADE] = Low). Hutchinson's sign demonstrated moderate sensitivity (52.6%; 12 studies, 847 patients, GRADE = Very Low), high specificity (89.2%; 12 studies, 1122 patients, GRADE = Low), moderate accuracy (67.8%; 12 studies, 1969 patients, GRADE = Very Low), high PPV (88.5%; 13 studies, 997 patients, GRADE = Low), and moderate NPV (59.8%; 12 studies, 1576 patients, GRADE = Very Low) for ocular involvement. Risk of bias was predominantly moderate, and certainty of evidence ranged from very low to low. Very low to low-certainty evidence supports HS as a predictive factor for ocular involvement in HZO. Its high specificity and PPV reinforce its clinical utility in risk stratification; however, its absence alone does not reliably exclude ocular complications. The author(s) have no proprietary or commercial interest in any materials discussed in this article.