Treat HSK Based on Clinical Findings, Not PCR Results, Researchers Argue

Published on August 15, 2025
Patients with suspected HSK who have undergone ocular or corneal surgery, as well as those with glaucoma or diabetes, were found to have a higher risk of poor clinical outcomes, suggesting that these individuals require closer monitoring. Photo: Nathan Morrow, OD. Click image to enlarge. Diagnosis of herpes simplex keratitis can be challenging, as its clinical manifestations vary widely. Although polymerase chain reaction (PCR) testing is regarded as the gold standard for diagnosis, it cannot solely confirm the presence of the disease and delaying intervention to obtain lab results is usually not advisable, underscoring the importance of basing treatment decisions on clinical findings. A new study conducted in Germany aimed to analyze herpes simplex virus (HSV)-PCR positivity rates and the impact of comorbidities on clinical outcomes in patients with corneal pathologies, including keratitis, persistent epithelial defects and corneal ulcers. Its findings revealed a high rate of comorbidities among the cohort; of these, previous ocular and corneal surgery, glaucoma and diabetes were correlated with poor outcomes.The retrospective study involved 194 eyes from 259 patients seen at a hospital in Berlin. All eyes were suspected to have HSK based on symptoms consistent with the condition, corneal erosions and ulcers, and each received PCR testing to detect the presence of HSV type 1 DNA. Patients also underwent measurements of BCVA, intraocular pressure and clinical manifestations observed through slit lamp examination. With a main aim to correlate clinical outcomes with both ocular and systemic comorbidities, the study defined a poor outcome as a final visual acuity greater than 0.4logMAR (20/50) or necessitating at least one corneal surgery.Results indicated that HSV-1 DNA was only detected in 36 out of the 194 eyes examined, equating to a positivity rate of 18.6%. Complications observed during the study included corneal scarring in 28.8% of cases and persistent epithelial defects in 8.5%, with a recurrence rate of 11.6% documented three months post-sampling.Comorbidities were prevalent among the cohort, with 77.8% containing at least one ocular comorbidity, including previous ocular and corneal surgeries (32% and 19.1%, respectively), blepharitis (26.3%) and glaucoma (11%). Systemic comorbidities were also fairly common; atopic diseases were recorded in 10.8% of cases, systemic immunosuppression in 9.3% and diabetes in 8.8%.Treatment regimens varied, with 41% of patients receiving systemic antiviral therapy, primarily oral acyclovir, and approximately 46% undergoing topical steroid treatment. The mean BCVA significantly improved from 0.94logMAR (20/175) at baseline to 0.78logMAR (20/120) after follow-up. The following comorbidities were associated with poor clinical outcomes: history of ocular and corneal surgery, glaucoma and diabetes mellitus.The varying sensitivity of different PCR methods could help explain the discrepancy between clinical suspicion rate and rate of positive HSK-PCR results, the researchers wrote in their paper on the study for Journal of Ophthalmic Inflammation and Infection. They pointed out, “The main specimen type in our study was corneal smears, which contain hardly any corneal tissue, making the sensitivity of the PCR testing low compared to the PCR-sensitivity to HSK using corneal scrapings or corneal buttons after keratoplasty.” The researchers made several recommendations for the clinical management of HSK based on these findings. For one, they advise eye doctors to treat the condition based on clinical evidence, even in the absence of positive PCR results, as underlying comorbidities can complicate the clinical picture and worsen the patient’s prognosis. Secondly, they argue, “Patients with suspected HSK who underwent ocular or corneal surgery and those with glaucoma and diabetes mellitus should be closely monitored due to the risk of a poor outcome.” Click here for the journal source. Dandachli MH, Maier AKB, Hofmann J, et al. Comorbidities, clinical outcome and rate of herpes simplex positive PCR in patients with keratitis, corneal erosions and ulcers. J Ophthal Inflamm Infect. August 7, 2025. [Epub ahead of print]. This article was developed by the editorial staff in conjunction with experts in the field. In the process, AI may have been among the editorial tools used to meet the goals of human editors, who approved all content.