Corneal endothelial cell loss confirmed in herpetic keratitis eyes, regardless of disease depth

Does herpetic keratitis cause measurable damage to the corneal endothelium beyond what is visible on clinical examination, and does the depth of corneal involvement determine the degree of endothelial compromise? A cross-sectional comparative study employing specular microscopy found that eyes affected by herpetic keratitis demonstrated significantly lower endothelial cell density and altered morphology compared with their contralateral clinically unaffected eyes, according to findings published in BMC Ophthalmology.¹

Singh and colleagues, of the Department of Ophthalmology at Maharajgunj Medical Campus, B.P. Koirala Lions Centre for Ophthalmic Studies, Tribhuvan University, Kathmandu, Nepal, conducted a hospital-based cross-sectional comparative study of 39 patients with clinically diagnosed unilateral herpes simplex keratitis.¹ Each participant contributed one affected eye and one contralateral unaffected fellow eye, yielding 78 eyes for analysis. Patients were enrolled consecutively from the cornea clinic using predefined inclusion and exclusion criteria, and all underwent non-contact specular microscopy using the NIDEK CEM-530, with endothelial cell density (ECD), coefficient of variation (CV), percentage of hexagonal cells and central corneal thickness (CCT) recorded automatically by device software.

What the specular microscopy data showed

Of the 39 patients, 29 (74%) presented with stromal keratitis and 10 (26%) with epithelial keratitis.¹ The cohort had a mean age of 46.33 ± 18.90 years and comprised 23 (59%) male and 16 (41%) female participants. Mean ECD was significantly lower in affected eyes than in contralateral unaffected eyes (2555.38 ± 474.05 vs 2879.00 ± 270.26 cells/mm², P < .001). The CV was significantly higher in affected eyes (34.92 ± 6.35% vs 29.77 ± 6.57%, P < .001), indicating greater variability in endothelial cell size, and the percentage of hexagonal cells was significantly lower (61.10 ± 5.04% vs 66.82 ± 3.97%, P = .02). CCT did not differ significantly between affected and unaffected eyes (538.08 ± 40.41 vs 546.26 ± 56.60 μm, P = .32). A sensitivity analysis excluding two outlier cases with markedly reduced ECD confirmed the overall findings remained statistically significant (P < .001).¹

Does it matter whether the keratitis is epithelial or stromal?

A subgroup analysis comparing ECD between epithelial and stromal keratitis groups found no statistically significant difference (2459.80 ± 516.27 vs 2588.34 ± 463.61 cells/mm², P = .47).¹ The authors noted this is consistent with prior confocal and specular microscopy studies demonstrating ECD reductions across the full clinical spectrum of herpetic keratitis, supporting the view that endothelial damage in herpes simplex virus-related disease is not strictly determined by the depth of corneal involvement.² The morphologic changes observed—increased cell size variability and reduced hexagonality—are indicative of compensatory enlargement and shape distortion of surviving endothelial cells following cell loss.¹

Clinical and surgical implications

The authors concluded that the findings highlight the utility of specular microscopy for identifying early or subclinical endothelial compromise in patients with herpetic keratitis, with particular relevance to surgical planning.¹ Increased cellular size variability and loss of normal endothelial morphology indicate reduced endothelial reserve and greater susceptibility to decompensation during intraocular procedures including cataract surgery and penetrating keratoplasty. In eyes with herpetic corneal scarring, graft survival has been shown to depend heavily on endothelial health, with chronic endothelial loss recognized as a contributor to late graft failure. The authors called for larger longitudinal studies to clarify the progression of endothelial changes over time and to inform decisions around the timing and nature of future surgical intervention.¹

Several limitations warrant acknowledgement, including a relatively small sample size, restriction of endothelial assessment to central corneal measurements, and the cross-sectional design, which precludes evaluation of longitudinal or progressive changes. Detailed clinical severity parameters such as symptom duration, corneal sensation and antiviral history were not evaluated, and the use of contralateral eyes as controls may introduce inter-eye correlation effects.¹

The authors declared no competing interests. The study received no external funding. Ethics approval was obtained from the Institutional Review Committee of Maharajgunj Medical Campus, Tribhuvan University.

References

1. Singh BK, Sitaula S, Bhattarai S, Joshi ND, Jha P. Corneal endothelial morphology in patients with herpetic keratitis attending tertiary eye centre. BMC Ophthalmol. 2026;26(1):451. Published 2026 Jul 30. doi:10.1186/s12886-026-05174-0

2. Hillenaar T, Weenen C, Wubbels RJ, Remeijer L. Endothelial involvement in herpes simplex virus keratitis: an in vivo confocal microscopy study. Ophthalmology. 2009;116(11):2077-86.e862. doi:10.1016/j.ophtha.2009.04.022